Here, to evaluate the effect of MGMT methylation on response, survival, and tolerance of TMZ treatment, we examined MGMT gene silencing by methylation of its promoter using the COBRA (combined bisulphite restriction analysis) technique in melanoma biopsies from 122 patients with metastatic melanoma who had been treated with TMZ in two large DeCOG (Dermatologic Cooperative Oncology Group) multicenter studies. This evidence concerns the gene MGMT and metastatic melanoma.