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CMM shares risk factors associated with UVR sensitivity with keratinocyte cancer (KC). CMM risk is dominated by <jats:italic>MC1R<\/jats:italic>, a gene regulating the proportions of black and red melanin produced. An emerging mutagenic mechanism involves reactive melanin, particularly red pheomelanin, that can itself induce DNA adducts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Demographically, epidemiologically, and mechanistically, pigmentation status is central to CMM risk and a shared genetic susceptibility, comprising several pigmentation genes, between CMM and KCs. In the general population, CMM risk is associated with pale skin and poor tanning ability, mechanistically due to a relative lack of protection against UVR adduct formation, or perhaps via an alternate manner in individuals with abundant pheomelanin. 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