We present an LS family in which all six tested members carried EpCAM c.344T>C, MSH2 c.2744A>G, PMS2 c.1408C>T, and APC c.5465T>A co-mutations, with the proband’s CRC tissue showing large deletions of EpCAM (exons 8–9) and MSH2 (exons 1–16). The gene discussed is MSH2; the disease is colorectal carcinoma.