The siblings’ age at CRC diagnosis, the family history with an absence of early onset malignancies in both parents, and the PMS2 expression loss in the neoplastic cells of both siblings’ tumors and in non-neoplastic cells of the index patient strongly suggested that they have CMMRD, although they had no non-neoplastic CMMRD features and PMS2 was expressed in the tumor-infiltrating immune cells of both siblings. The gene discussed is PMS2; the disease is neoplasm.