A study showed that a significant proportion of patients with Bethesda criteria who have loss of MLH1 protein expression in their tumors and do not have an MLH1 pathogenic germline mutation display constitutional MLH1 methylation as the mechanism of Lynch syndrome, especially patients with CRC diagnosed before age 50, with multiple Lynch syndrome-associated tumors and no significant family history of early-onset disease [23]. The gene discussed is MLH1; the disease is Lynch syndrome.