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The incidence of melanoma has dramatically risen over the past several decades and in 2013, an estimated 76,690 new cases and 9,480 deaths were expected in the United States (1). As a result, melanoma is now the fifth and sixth most common malignancy in the United States among men and women, respectively (1).


Risk factors for melanoma include light complexion, poorly tanning skin, and blonde or red hair, which confer a relative risk of 1.3–4.1 (2). Intense, intermittent sun exposure and a history of blistering sunburn appear to confer a greater risk than lower-level, continuous sunlight exposure (3). Both ultraviolet A (UVA) and ultraviolet B (UVB) radiation have been implicated in the pathogenesis of melanoma (4). Exposure to UV radiation via tanning booths and, with psoralen, as a treatment for psoriasis, is associated with an increase in the risk of melanoma (5).

Numerous common nevi are a marker of increased risk, as are atypical nevi (6). Large congenital nevi have a high risk of malignant transformation (lifetime risk 4%–10%) (7,8,9). Following the diagnosis of melanoma, the probability of developing a second primary melanoma has been estimated to be 5.34% over an interval of 20 years (10).

Melanoma in a first-degree relative confers an increased risk, and about 10% of individuals diagnosed with melanoma have an affected family member (11, 12). However, the magnitude of the risk associated with family history is quite variable. Most families with multiple affected members have no identifiable genetic abnormality. Genes in which germline mutations or polymorphisms have been associated with an increased risk of melanoma include CDKN2A and CDK4, which encode cell cycle regulatory proteins, the melanocortin 1 receptor gene, and the breast cancer susceptibility gene, BRCA2 (relative risk for melanoma, 2.58) (13,14,15,16).

The dysplastic nevus syndrome is characterized by numerous atypical nevi and the development of melanoma at an early age (17). The lifetime risk of melanoma approaches 100% in this syndrome. Its genetic basis remains unknown.


The majority of melanomas display at least one of the following features:

  • A: Asymmetry

  • B: Irregularity of borders

  • C: Color variegation

  • D: Diameter >6 mm

  • E: Enlargement or evolution

Ten percent of incident cases of melanoma are classified as having nodular histology and, therefore, lack the characteristic asymmetry, irregularity of border, and color variegation of the more common superficial spreading melanoma. However, nodular melanomas are associated with the poorest survival of all subtypes and account for a disproportionate number of melanoma deaths (18).


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