Because colorectal tumors characterized by MSI are distinct from MSS tumors in many molecular aspects, such the association with the methylator phenotype, which is responsible for MLH1 methylation, the higher frequency of BRAF mutations and the lower frequencies of KRAS, APC and TP53 mutations, MSI and MSS colon cancers represent tumors with a different molecular background. This evidence concerns the gene MLH1 and colorectal neoplasm.