Melanoma: Complete Guide

Written by: Catherine Brooks, MD

Reviewed by: Dr. Paul Anderson, Dermatologic Oncologist

Last reviewed: January 24, 2026

Quick Facts

Most dangerous form of skin cancer
5th most common cancer in the US
99% 5-year survival when caught early (localized)
Can spread to any organ in the body
Immunotherapy has revolutionized treatment
90% of melanomas are caused by UV exposure
Can occur in areas not exposed to sun
Average age at diagnosis: 65 years

What is Melanoma?

Melanoma is a type of skin cancer that develops from melanocytes, the cells that produce melanin (the pigment that gives skin its color). While less common than basal cell and squamous cell skin cancers, melanoma is more dangerous because of its ability to spread to other organs if not caught early.

Key Points

Melanoma accounts for only 1% of skin cancers but causes most skin cancer deaths
Can develop anywhere on the body, including areas not exposed to sun
May arise from existing moles or appear as new lesions
Early detection dramatically improves outcomes
Treatment has been transformed by immunotherapy and targeted therapy

Where Melanoma Develops

Men: Most common on trunk (chest and back)
Women: Most common on legs
Older adults: Face, neck, ears
Dark skin: Palms, soles, under nails, mucous membranes
Rare sites: Eye (uveal), mucous membranes, internal organs

Types of Melanoma

Cutaneous Melanoma Subtypes

Superficial Spreading Melanoma (70%)

Most common type
Spreads along skin surface before growing deeper
Often develops from existing mole
Can occur anywhere on body

Nodular Melanoma (15-20%)

Most aggressive common type
Grows vertically into skin quickly
Usually appears as raised, dark bump
Can be amelanotic (lacking pigment)

Lentigo Maligna Melanoma (10-15%)

Develops from lentigo maligna (in situ melanoma)
Common in elderly on sun-damaged skin
Usually on face, ears, arms
Slow-growing initially

Acral Lentiginous Melanoma (5%)

Most common melanoma in dark-skinned individuals
Appears on palms, soles, under nails
Not related to sun exposure
Often diagnosed late due to location

Other Types

Desmoplastic melanoma: Rare, fibrous, often amelanotic
Uveal melanoma: In the eye
Mucosal melanoma: In mucous membranes
Melanoma of unknown primary: Metastatic without known primary

Special Variants

Amelanotic melanoma: Lacks pigment, pink or flesh-colored
Spitzoid melanoma: Resembles Spitz nevus
Nevoid melanoma: Resembles benign nevus

Signs and Symptoms

The ABCDE Guide for Melanoma Detection

A - Asymmetry: One half doesn't match the other
B - Border: Irregular, ragged, notched, or blurred edges
C - Color: Multiple colors (brown, black, tan, red, white, blue)
D - Diameter: Larger than 6mm (pencil eraser), though can be smaller
E - Evolving: Changes in size, shape, color, or symptoms

Additional Warning Signs

New pigmented lesion after age 30
Lesion that looks different from other moles ("ugly duckling" sign)
Sore that doesn't heal
Pigmentation spreading from border
Redness or swelling beyond border
Itching, tenderness, or pain
Surface changes: oozing, bleeding, scaly appearance
Satellite lesions (small spots near main lesion)

Symptoms of Advanced Melanoma

Hard lumps under skin (lymph nodes)
Fatigue
Unexplained weight loss
Headaches (brain metastases)
Seizures
Bone pain
Abdominal pain (liver metastases)
Shortness of breath (lung metastases)

⚠️ See a Dermatologist Immediately If:

Any new or changing pigmented lesion
Mole that bleeds or won't heal
Rapidly growing pigmented lesion
Multiple new moles appearing
Any lesion with ABCDE features

Causes and Risk Factors

Primary Cause

UV radiation: From sun or tanning beds
- Causes DNA damage in melanocytes
- Both UVA and UVB contribute
- Intermittent intense exposure (sunburns) highest risk

Major Risk Factors

Fair skin: Less melanin = less UV protection
History of sunburns: Especially blistering sunburns in childhood
Excessive UV exposure: Sun or tanning beds
Many moles: >50 common moles or atypical moles
Family history: 10% have family member with melanoma
Personal history: Previous melanoma or other skin cancers
Weakened immune system: Immunosuppression, HIV, organ transplant
Age: Risk increases with age, but common in young adults too

Genetic Risk Factors

CDKN2A mutations: 40% lifetime risk
CDK4 mutations: Rare
BAP1 mutations: Also increases uveal melanoma risk
MC1R variants: Red hair gene
Familial atypical mole-melanoma syndrome (FAMMM)
Xeroderma pigmentosum: Defective DNA repair

Physical Characteristics

Light eye color (blue, green)
Red or blonde hair
Freckling tendency
Inability to tan
Dysplastic nevi (atypical moles)
Giant congenital melanocytic nevi

Diagnosis

Clinical Examination

Full-body skin examination
Dermoscopy (dermatoscope examination)
Photography for monitoring
Lymph node palpation

Biopsy Types

Excisional biopsy (preferred): Removes entire lesion with narrow margin
Punch biopsy: For large lesions, multiple punches may be needed
Shave biopsy: Generally avoided, may miss depth
Incisional biopsy: For very large lesions

Pathology Report Information

Breslow thickness: Most important prognostic factor
Ulceration: Presence worsens prognosis
Mitotic rate: Cell division rate
Clark level: Depth of invasion (less used now)
Margins: Clear or involved
Regression: Signs of immune response
Lymphovascular invasion: Cancer in vessels
Neurotropism: Growth along nerves
Satellites: Separate tumor deposits

Molecular Testing

BRAF mutation: Present in 50% of melanomas
NRAS mutation: 15-20%
KIT mutation: Acral and mucosal melanomas
NF1 mutation: 10-15%
Triple wild-type: No BRAF/NRAS/NF1 mutations

Staging Workup

Sentinel lymph node biopsy: For tumors >0.8mm or with high-risk features
CT scan: Chest, abdomen, pelvis for stage III/IV
PET/CT: More sensitive for metastases
Brain MRI: For stage III/IV or symptoms
LDH level: Prognostic marker

Staging

TNM Classification (8th Edition)

Stage	Primary Tumor (T)	Nodes (N)	Metastasis (M)	5-Year Survival
Stage 0	In situ	N0	M0	99%+
Stage IA	≤1mm, no ulceration	N0	M0	99%
Stage IB	≤1mm with ulceration OR 1-2mm no ulceration	N0	M0	97%
Stage IIA	1-2mm with ulceration OR 2-4mm no ulceration	N0	M0	94%
Stage IIB	2-4mm with ulceration OR >4mm no ulceration	N0	M0	87%
Stage IIC	>4mm with ulceration	N0	M0	82%
Stage IIIA	≤1mm	N1a or N2a (microscopic)	M0	93%
Stage IIIB	Various	N1a/b or N2a/b	M0	83%
Stage IIIC	Various	N2b/c or N3	M0	69%
Stage IIID	>4mm with ulceration	N3	M0	32%
Stage IV	Any	Any	M1	30%*

*Stage IV survival has improved dramatically with new treatments

Breslow Thickness Categories

Thin: ≤1.0 mm
Intermediate: 1.01-4.0 mm
Thick: >4.0 mm

Treatment Options

Surgery

Wide Local Excision

Surgical margins based on Breslow thickness:

In situ: 0.5-1 cm margins
≤1 mm: 1 cm margins
1.01-2 mm: 1-2 cm margins
>2 mm: 2 cm margins

Sentinel Lymph Node Biopsy (SLNB)

Recommended for tumors >1 mm
Consider for 0.8-1 mm with high-risk features
Identifies microscopic nodal disease
Prognostic information

Complete Lymph Node Dissection

For clinically positive nodes
Controversial for positive sentinel nodes
May be avoided with close monitoring

Adjuvant Therapy (Post-Surgery)

Stage IIB/IIC

Pembrolizumab for 1 year
Nivolumab under investigation
Clinical trials

Stage III

Immunotherapy:
- Nivolumab for 1 year (preferred)
- Pembrolizumab for 1 year
Targeted therapy (BRAF-mutated):
- Dabrafenib + trametinib for 1 year

Advanced/Metastatic Disease

First-Line Immunotherapy

Single-agent:
- Pembrolizumab
- Nivolumab
Combination:
- Nivolumab + ipilimumab (higher response rate, more toxicity)
- Nivolumab + relatlimab (LAG-3 inhibitor)

Targeted Therapy (BRAF V600 Mutated)

Dabrafenib + trametinib
Vemurafenib + cobimetinib
Encorafenib + binimetinib

Second-Line Options

Switch between immunotherapy and targeted therapy
Ipilimumab monotherapy
Clinical trials
Chemotherapy (rarely used)

Other Treatments

Radiation Therapy

Brain metastases (stereotactic radiosurgery)
Symptomatic bone metastases
Adjuvant for high-risk features
Palliative for bleeding/pain

Intralesional Therapy

Talimogene laherparepvec (T-VEC) - oncolytic virus
For accessible lesions
Can combine with immunotherapy

Regional Therapy

Isolated limb perfusion
Isolated limb infusion
For in-transit metastases

The Immunotherapy Revolution

Game-Changing Impact

Immunotherapy has transformed melanoma from one of the deadliest cancers to one with potential for long-term survival even in advanced stages.

Checkpoint Inhibitors

PD-1 Inhibitors

Pembrolizumab (Keytruda):
- Response rate: 35-45%
- 5-year survival: 35-40% in metastatic disease
Nivolumab (Opdivo):
- Similar efficacy to pembrolizumab
- Can combine with ipilimumab

CTLA-4 Inhibitor

Ipilimumab (Yervoy):
- First checkpoint inhibitor approved
- Usually combined with nivolumab now
- Higher toxicity

LAG-3 Inhibitor

Relatlimab: Combined with nivolumab (Opdualag)

Response Patterns

Complete response: 5-10% with monotherapy, 20% with combination
Durable responses: Many last years
Pseudoprogression: Initial growth before shrinkage (rare)
Hyperprogression: Rapid growth (rare)

Immune-Related Adverse Events

Dermatitis (rash, pruritus)
Colitis (diarrhea)
Hepatitis
Pneumonitis
Endocrinopathies (thyroid, pituitary, adrenal)
Nephritis
Neurologic toxicities (rare)
Myocarditis (rare but serious)

Prognosis and Survival

Overall Survival Rates

5-year overall survival: 94%
10-year overall survival: 89%

Factors Affecting Prognosis

Primary Tumor Factors

Breslow thickness (most important)
Ulceration
Mitotic rate
Location (extremities better than trunk/head/neck)
Gender (women have better prognosis)

Nodal Factors

Number of positive nodes
Microscopic vs. macroscopic disease
Extracapsular extension

Metastatic Factors

Site of metastases (skin/nodes better than visceral)
Number of metastatic sites
LDH level
BRAF mutation status

Long-term Outcomes with Modern Therapy

Stage III: 5-year survival now >70% with adjuvant therapy
Stage IV: 5-year survival approaching 50% with immunotherapy
Some patients achieve durable complete remissions

Prevention and Screening

☀️ Sun Protection Guidelines

Use broad-spectrum sunscreen SPF 30+ daily
Reapply every 2 hours when outdoors
Seek shade between 10 AM - 4 PM
Wear protective clothing, wide-brimmed hats
Wear UV-blocking sunglasses
Avoid tanning beds completely

Primary Prevention

Start sun protection in childhood
Use sunscreen even on cloudy days
Be aware of reflection from water, snow, sand
Check UV index before outdoor activities
Extra caution with photosensitizing medications

Screening Recommendations

Self-Examination

Monthly full-body skin checks
Use mirrors for hard-to-see areas
Have partner check scalp and back
Photograph moles for comparison
Use ABCDE criteria

Professional Screening

Average risk: Annual skin exam by dermatologist
High risk: Every 3-6 months
Very high risk: Every 3 months with photography

High-Risk Individuals Requiring Closer Surveillance

Personal history of melanoma
Family history of melanoma
Atypical mole syndrome
>50 common moles
History of severe sunburns
Immunosuppression
Genetic predisposition

Follow-up Care

Surveillance Schedule

Stage 0-IA

Every 6-12 months for 5 years
Then annually
Self-exams monthly

Stage IB-II

Every 3-6 months for 2 years
Every 6 months for years 3-5
Then annually
Consider imaging for IIC

Stage III-IV (NED)

Every 3-4 months for 2 years
Every 6 months for years 3-5
Then annually
Regular imaging (CT/PET)
Brain MRI periodically

What Follow-up Includes

Complete skin examination
Lymph node palpation
Review of symptoms
Laboratory tests as indicated
Imaging based on stage and symptoms
Patient education on self-examination

Survivorship Care

Sun protection counseling
Psychosocial support
Management of treatment effects
Screening for second primary melanomas
Family member screening recommendations

Frequently Asked Questions

Can melanoma be cured?

Yes, when caught early. Stage I melanoma has a 99% 5-year survival rate. Even advanced melanoma can now achieve long-term remissions with immunotherapy and targeted therapy.

Does melanoma always start from a mole?

No. About 70% of melanomas arise in normal skin as new lesions. Only 30% develop from existing moles. This is why new pigmented lesions in adults need evaluation.

Can dark-skinned people get melanoma?

Yes, though less common. In darker skin, melanoma often occurs on palms, soles, or under nails (acral lentiginous type) and is often diagnosed later, leading to worse outcomes.

Are tanning beds really dangerous?

Yes. Using tanning beds before age 35 increases melanoma risk by 75%. There is no "safe" tan from UV exposure—any tan indicates skin damage.

Should all moles be removed?

No. Only moles that are changing, symptomatic, or atypical need removal. Most moles are benign and don't require treatment. Regular monitoring is key.

Is melanoma hereditary?

About 10% of melanomas occur in people with family history. Having a first-degree relative with melanoma doubles your risk. Genetic testing may be appropriate for families with multiple cases.

What's the difference between melanoma and other skin cancers?

Melanoma arises from melanocytes and is more aggressive than basal cell or squamous cell carcinomas. It's more likely to spread but accounts for only 1% of skin cancers.

Can melanoma come back after treatment?

Yes. Risk of recurrence depends on initial stage. Most recurrences happen within 2-3 years, but late recurrences can occur. Lifelong surveillance is important.

What is immunotherapy and how does it work?

Immunotherapy drugs remove the "brakes" on your immune system, allowing it to recognize and attack cancer cells. This has revolutionized melanoma treatment with long-lasting responses.

Should I avoid sun completely?

No, moderate sun exposure with protection is fine and vitamin D is important. The goal is to prevent sunburn and excessive UV exposure, not avoid outdoors entirely.

Sources

National Cancer Institute. Melanoma Treatment (PDQ) - Health Professional Version. Updated January 2026.
American Cancer Society. Melanoma Skin Cancer Statistics. 2026.
NCCN Clinical Practice Guidelines. Melanoma. Version 1.2026.
Swetter SM, et al. NCCN Guidelines Insights: Melanoma. J Natl Compr Canc Netw. 2025.
American Academy of Dermatology. Melanoma: Diagnosis and Treatment. 2025.
Long GV, et al. Cutaneous melanoma. Lancet. 2025.
ASCO Guidelines. Management of Stage III Melanoma. 2025 Update.