An in silico screening of 12 Caffeine Molecular Targets (CMT) obtained from published reports on Pubmed indicated eight genes, namely DNA2, MAPK1, PTK2B, ADORA2A, MAOA, PARP1, TYR, and HDAC1, whose expression was significantly changed in melanoma specimens compared to nevi, and with highly interesting AUC. This evidence concerns the gene HDAC1 and melanoma.