The microsatellite instability (MSI) phenotype is induced by deficient MMR (dMMR) function resulting from germline mutation in at least one of the MMR genes (MLH1, MSH2, PMS2, and MSH6) or epigenetic inactivation of MLH1. Moreover, 5%–15% of patients with CRC suffer from dMMR/MSI colorectal cancer (7), which exhibits indolent clinical behavior, including more proximal and poorly differentiated tumors, resistance to treatment with 5-FU, and better relapse-free survival (RFS) but poor overall survival after relapse (8–10). Here, MSH6 is linked to colorectal cancer.