POLE/D1 ED-associated signatures were detectable in the POLD1 p.Asp316His carrier’s CRC tumor (signature 10 contribution: 20.66%), but barely identifiable in the POLD1 p.Asp316Gly carrier’s liver metastasis (signature 10: 0.75%; signature 20 [POLD1 + MMR deficiency]: 2.65%) or in the POLE p.Leu424Val carrier’s oligodendroglioma (signature 14 [POLE + MMR deficiency]: 4%), where MMR deficiency hoarded most of the mutational signatures’ contribution. This evidence concerns the gene POLE and colorectal carcinoma.