Microsatellite-instability-high (MSI-H) cancers are a unique class of tumors that may arise from somatic inactivating mutations or epigenetic silencing of mismatch repair (MMR) pathway genes, namely, mutL homologue 1 (MLH1), mutS homologue 2 (MSH2), mutS homologue 6 (MSH6), and postmeiotic segregation increased 2 (PMS2), or from germline mutations in the mismatch repair pathway genes. This evidence concerns the gene PMS2 and cancer.