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  • May be flat or raised with irregular borders.

  • Examination may show varying colors, including red, white, black, and blue.

  • Should be suspected in any pigmented skin lesion with recent change in appearance.

  • Less than 30% develop from existing moles.


Malignant melanoma, the fifth most common of all cancers in the United States, is the leading cause of death due to skin disease and has doubled in incidence over the past 30 years. In 2021, approximately 106,110 new melanomas were diagnosed in the United States, with approximately 60% in men. In 2021, melanoma caused an estimated 7180 deaths (two-thirds in men). The lifetime risk of melanoma is 2% in White individuals and 0.1–0.5% in non-White persons. One in four cases occurs before age 40. Increased detection of early melanomas has led to increased survival, but fatalities continue to increase, especially in men older than 70 years.

Tumor thickness is the single most important prognostic factor. Ten-year survival rates related to melanoma thickness are less than 1 mm, 95%; 1–2 mm, 80%; and 2–4 mm, 55%. The 5-year survival rate is 62% with lymph node involvement and 16% with distant metastases.


Primary malignant melanomas may be classified into various clinicohistopathologic types, including lentigo melanoma (arising on chronically sun-exposed skin of older individuals); superficial spreading melanoma (two-thirds of all melanomas arising on intermittently sun-exposed skin); nodular melanoma; acral-lentiginous melanomas (arising on palms, soles, and nail beds); ocular melanoma; and melanomas on mucous membranes. Different types of melanoma appear to have distinct oncogenic mutations, which may be important in the treatment of patients with advanced disease. Less than 30% of melanomas develop from existing moles. Clinical features of pigmented lesions suspicious for melanoma are an irregular, notched border where the pigment appears to be spreading into the normal surrounding skin and irregular surface topography (ie, partly raised and partly flat) (Figure 6–5 and eFigure 6–7). Color variegation is present and is an important indication for referral. A useful mnemonic is the ABCDE rule: Asymmetry, Border irregularity, Color variegation, Diameter greater than 6 mm, and Evolution (eFigure 6–8). The history of a changing mole (evolution, including bleeding and ulceration) is the single most important historical reason for close evaluation and possible referral. A mole that appears distinct from the patient’s other moles deserves special scrutiny—the “ugly duckling sign.” A patient with a large number of moles is statistically at increased risk for melanoma and deserves annual total body skin examination by a primary care clinician or dermatologist, particularly if the lesions are atypical in appearance.

eFigure 6–7.

Melanoma resembling a seborrheic keratosis on the lateral face of a man. (Reproduced with permission from Richard P. Usatine, MD, in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley HS. The Color Atlas and Synopsis ...

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