We conclude that a significant proportion of patients with Bethesda criteria who have loss of MLH1 protein expression in their tumors and do not have a MLH1 pathogenic germline mutation, display constitutional MLH1 methylation as the mechanism of Lynch syndrome, especially in patients with CRC diagnosed before the age of 50 years, with multiple Lynch syndrome‐associated tumors, and no significant family history of early‐onset disease. This evidence concerns the gene MLH1 and colorectal carcinoma.