High-penetrance germline mutations in CDKN2A, CDK4 and BAP1 disrupt critical tumor-suppressor pathways, while variants in MC1R, encoding the α-melanocyte-stimulating hormone receptor, modulate pigmentation and are associated with UV-related mutagenesis; loss-of-function MC1R polymorphisms, commonly found in individuals with low phototype characterized by fair skin, red/blond hair, light-colored eyes, and freckling, further increase melanoma risk [8,9,10]. This evidence concerns the gene MC1R and melanoma.