Polymerase proofreading-associated polyposis (PPAP; MIM 615083 and 612591) is caused by POLE (MIM *174762) and POLD1 (MIM *174761) exonuclease domain PVs and is characterized by the development of polyposis and CRC, as well as other cancers, in adulthood with a median age at CRC diagnosis of 41 and 43 years for POLD1 PV and POLE PV carriers, respectively [15]. The gene discussed is POLE; the disease is colorectal carcinoma.