Temozolomide itself has been shown to partially deplete the extent of expression of MGMT protein in tumor specimens of one patient affected by metastatic melanoma (2), possibly as a result of the inactivation and degradation of one molecule of MGMT protein each cycle of dealkylation of O6-MG, but the large series of clinical trials performed in patients affected by glioblastoma considering MGMT methylation indicated this mechanism is not sufficient in routinary clinical applications aimed to overcome the resistance to temozolomide in MGMT unmethylated glioma cells (38,47,58,60,71,74,75,86). The gene discussed is MGMT; the disease is metastatic melanoma.