Heterozygous carriers of constitutional pathogenic variants in the exonuclease domain of POLD1 are mainly predisposed to multiple adenomatous gastrointestinal polyps, as well as colorectal and endometrial cancers, among other tumor types, which largely overlap the phenotypic features of other autosomal dominant colorectal cancer predisposition syndromes associated with defects in DNA repair components, such as those caused by POLE proofreading deficiency or dMMR (Lynch syndrome). Here, POLD1 is linked to endometrial cancer.