Last reviewed: 8 May 2023
Last updated: 20 Jan 2023



History and exam

Key diagnostic factors

  • altered pigmented lesion (ABCDE signs)
  • melanocytic lesion that does not resemble surrounding melanocytic naevi ('ugly duckling')
  • spontaneous bleeding or ulceration of a pigmented lesion
  • constitutional symptoms
  • nail sign: persistent single-nail melanonychia striata
  • nail sign: Hutchinson's sign
  • atypical dermoscopy findings
  • fixed lymphadenopathy
  • in-transit metastases
More key diagnostic factors

Risk factors

  • family history of melanoma
  • personal history of melanoma
  • personal history of skin cancer (including actinic damage)
  • history of atypical naevi
  • Fitzpatrick skin type I or II (white skin)
  • red or blond hair colour
  • high freckle density
  • sun exposure
  • sun bed use
  • light eye colour
  • increased numbers of benign-appearing melanocytic naevi
  • large congenital naevi
  • immunosuppression
  • xeroderma pigmentosum
More risk factors

Diagnostic investigations

1st investigations to order

  • dermoscopy
  • skin biopsy
  • immunohistochemistry
More 1st investigations to order

Investigations to consider

  • sentinel lymph node biopsy
  • chest/abdominal/pelvic CT scan
  • whole-body PET scan
  • brain imaging (CT or MRI)
  • BRAF mutational analysis
  • NRAS mutational analysis
  • serum lactate dehydrogenase (LDH)
More investigations to consider

Emerging tests

  • CDKN2A mutational analysis

Treatment algorithm


early stage melanoma (melanoma in situ, stage I, stage II)

resectable advanced melanoma (stage III and stage IV)

unresectable advanced disease (stage III and stage IV)



Prachi Bhave, BE (Hons), MBBS, FRACP

Medical Oncologist

Peter MacCallum Cancer Centre




PB has received honoraria from Novartis and sponsorship from MSD and Novartis.

Yin Wu, MRCP, PhD

Wellcome Trust Clinical Research Career Development Fellow and Honorary Consultant Medical Oncologist

Peter Gorer Department of Immunobiology

King's College London

Department of Medical Oncology

Guy's and St Thomas' NHS Foundation Trust




YW is funded by the Wellcome Trust.

Pablo Fernandez-Peñas, MD, PhD, FACD

Associate Professor of Dermatology

The University of Sydney




PF-P declares that he has no competing interests with the topic Melanoma. PF-P has advisory roles with Amgen, Boehringer Ingelheim, Bristol Meyers Squibb, Leo, Novartis, Lilly, Abbvie, Janssen, Celgene (psoriasis, atopic eczema, hidradenitis), Roche, Merck Sharp & Dohme, Sun Pharmaceuticals, Novartis, and Sanofi. He has been paid to do research for Incyte Europe Sarl, and clinical trials for Arena, Akaal Pharma, Xoma, Kyowa Hakko Kirin, AbbVie, OncoSec, Lilly, CSL Behring, Boehringer Ingelheim, Pfizer, mRage, Eisai, Jiansu Hengrui, Bristol-Myers Squibb, Sun Pharma, Novartis, Roche, Galderma, Regeneron, UCB, GlaxoSmithKline, and Amgen.


Dr Prachi Bhave, Dr Yin Wu, and Dr Pablo Fernandez-Peñas would like to gratefully acknowledge Dr Robyn P.M. Saw, Dr Sophie E. Papa, Dr Alexander M. Menzies, Dr Philip Friedlander, Dr Hobart W. Walling, and Dr Brian L. Swick, previous contributors to this topic.


RPMS is on the advisory board for Novartis, MSD, and Qbiotics and has previously been on the advisory board for Amgen; he has received honoraria from BMS and Novartis. SEP has received honoraria from BMS, MSD, and Novartis to attend conferences; she has participated in advisory boards for BMS, MSD, Amgen, Roche, and GSK. AMM has received honoraria from Novartis and BMS; he is on the advisory boards of MSD and Chugai. PF is a consultant for Genentech. HWW and BLS declare that they have no competing interests.

Peer reviewers

David Cassarino, MD, PhD

Assistant Professor

Department of Pathology and Laboratory Medicine

University of California

Los Angeles



DC declares that he has no competing interests.

James DeBloom, MD

Dermatologist/Dermatologic Surgeon

President of the South Carolina Skin Cancer Center




JB declares that he has no competing interests.

Mai Brooks, MD, FACS

Associate Director

JCCC Women's Cancers Program Area

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles



MB declares that she has no competing interests.

Karol Sikora, MA, MBBCh, PhD, FRCR, FRCP, FFPM

Medical Director





KS declares that he has no competing interests.

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