Also known as Lynch syndrome (LS), the syndrome-associated cancer is inherited in an autosomal dominant manner in the family. Colorectal cancer (CRC) occurs earlier than in the general population, with a mean age of 45 years for LS and 69 years for the general population. It occurs in the proximal (right) colon, and approximately 70% of CRCs are located in the proximal splenic flexure where carcinogenesis is accelerated (very small adenomas can develop quickly into cancer), 2-3 years for LS and 8-10 years for the general population. CRCs are additionally at high risk for secondary primary tumor development within 10 years of surgery in 25-30% of patients with LS-associated CRC if the surgical resection is less than a subtotal resection of the colon. There is an increased risk of malignancy at certain extracolonic sites [4,5]: endometrium and ovary (40C60% and 12C15% lifetime risk for female mutation carriers, respectively), stomach (some families in some Asian countries have a high risk for unknown reasons), small intestine, hepatobiliary duct, pancreas, upper urinary tract epithelium (migratory cell carcinoma of the ureter and renal pelvis, especially LS-MSH2 type), brain (Turcot’s syndrome), MuirCTorre syndrome associated with multiple sebaceous adenomas, sebaceous carcinomas and keratoacanthomas. CRCs pathology is characterized by: common hypodifferentiated adenocarcinoma (indolent cell carcinoma) and mucinous adenocarcinoma; hypodifferentiated adenocarcinoma often has a well-defined border with massive lymphocytic infiltration or aggregation of lymphoid cells resembling Crohn’s reaction; tend to show swelling growth rather than infiltrative growth CRC survival rate is higher than the general population l More than 90% of tumors occurring in LS patients show high microsatellite instability. The final diagnosis relies on the detection of germline mutations in the MMR genes (MLH1, MSH2, MSH6, or PMS2), whereby family members are classified as carriers of mutations with a high risk of syndrome-associated carcinogenesis and normal mutation-free individuals.