The classical and considered to be the most important gene, accounting for 20–40% of predisposition for melanoma, is CDKN2A. It encodes two tumor suppressor proteins, p16 (INK4A) and p14 (ARF), that inhibit the cell cycle and enhance apoptosis through action on CDK4 [encoding cyclin-dependent protein kinase 4 (CDK4)] and inhibition of CDK6 kinases [13,30,99,101,102]. This evidence concerns the gene CDK4 and melanoma.