COMT has been implicated the protection of melanocytes from the cytotoxic dihydroxyindole derivatives that are formed during eumelanogenesis by O-methylation [31]; indeed, O-methylated forms of the eumelanin intermediates 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid have been detected in the urine and serum from human melanoma patients and melanoma-bearing mice [44,80–83]. This evidence concerns the gene COMT and melanoma.