Autosomal dominant inheritance of mutations in the INK4a/ARF locus or the CDK4 gene may confer a high risk of cutaneous melanoma development. The penetrance of INK4a/ARF mutations is influenced by UV exposure. Inherited variants in the melanocortin-1 receptor also confer increased risk of cutaneous melanoma. Features associated with increased genetic susceptibility to cutaneous melanoma include the presence of multiple affected first-degree relatives on one side of the family, multiple primary melanomas in the same individual, earlier age of onset, and the presence of multiple atypical nevi, but none of these factors reliably predicts for the presence of INK4a/ARF mutations. It is currently premature to offer predictive DNA testing for melanoma outside of defined research protocols. This is because of (1) the low likelihood of finding mutations in known melanoma susceptibility genes, even in more than 60% of melanoma-prone kindreds; (2) the broad confidence limits on current estimates of lifetime penetrance of INK4a/ARF mutations and the wide variation in this penetrance with locality; (3) a high "background" incidence of melanoma in non-mutation carriers in melanoma-prone families; (4) current uncertainties about the factors determining the functionality and phenotypic expression of the trait among carriers of these mutations (penetrance), even if found; and (5) the lack of proved efficacy of melanoma prevention and surveillance strategies, even for mutation carriers. Rather than singling out those deemed to be at high risk because of family history, all patients carrying risk factors for cutaneous melanoma should be subject to stringent programs of sun protection and skin surveillance.