Constitutional mismatch repair deficiency (CMMRD) is a highly penetrant cancer‐predisposition syndrome, caused by biallelic germline pathogenic variants affecting one of the four mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. CMMRD typically manifests in childhood or adolescence as one of a broad range of malignancies, primarily of the hematopoietic system and brain, as well as colorectal and other cancers associated with heterozygous germline MMR pathogenic variants (Lynch syndrome). The gene discussed is PMS2; the disease is Lynch syndrome.