The predictive value of MGMT methylation in response to temozolomide has reached over the years an overall confirmatory consensus, such that analysis of MGMT methylation has been included to stratify patients enrolled in major multicenter international clinical trials (38,47,58,60,71,74,75,86) and leading recommendations have been stated on how to treat patients affected by glioma, where the analysis of MGMT methylation is assumed as one of the key decision points in the therapeutic flow-chart (87). The gene discussed is MGMT; the disease is central nervous system cancer.