In the haplotype analysis of OCA2 (rs7497270, rs1800401, rs1800407, and rs1800414) and HERC2 (rs916977, rs7170852, and rs12913832), we observed that the TCCTTTA haplotype in males was associated with a protective effect against melanoma (OR = 0.14, 95% CI = 0.02–0.96). This evidence concerns the gene OCA2 and melanoma.