Today, guidelines recommend (i) screening all diagnosed colorectal and endometrial cancer patients for LS; (ii) excluding hypermethylation of the MLH1 promoter, MMR-D/MSI-H, CRC, and/or BRAF V6OOE mutation in the case of MLH1 and PMS2 expression; and (iii) offering patients genetic evaluations and possible confirmatory germline testing. This evidence concerns the gene MLH1 and colorectal carcinoma.