-Activated caspase-8, caspase-9, and caspase-10 are involved in apoptotic cell death and the cytotoxic effect of the combined treatment of melanoma.-The genotypes of CASP8 D302H and CASP8 -652 6N variants are associated with melanoma risk in single-locus analysis, and the combined genotypes of CASP8 and CASP10 polymorphisms may be biomarkers of melanoma susceptibility.-The SNP variants CASP8 D302H, CASP8 -652 6N, and CASP10 I522L and their haplotypes influence melanoma risk in multivariate analysis. This evidence concerns the gene CASP8 and melanoma.