In supporting of the contribution of MGMT protein in MSI-H pathway of CRC neoplasia, Svrcek et al. reported that field defects resulted from MGMT loss are more frequently associated with MSI-H than microsatellite-stable (MSS) colorectal cancers and concluded that methylation tolerance may represent a crucial initiating step prior to MMR deficiency in the development of MSI-H CRC (24). This evidence concerns the gene MGMT and colorectal cancer.