Among these one, the gene of Adenomatous Polyposis Coli (APC) (16%), Cadherin 13 (CDH13) (16%), Estrogen Receptor 1 (ESR1) (14%), Cyclin-dependent kinase inhibitor 2A (CDKN2A) (6%), and Ras association domain-containing protein 1 (RASSF1) (5%), were the most methylated, while Retinoic acid receptor (RARB) accounted for 31% of the most frequently methylated genes; these results indicated a noteworthy pattern of methylation-induced gene silencing in melanoma. This evidence concerns the gene CDKN2A and melanoma.