In the last decade, different new genes have been identified to be associated with colon polyposis predisposition (GREM1, MBD4, MLH3, MSH3, NTHL1, POLD1, POLE, and RNF43), each of which explains only a very small proportion of patients with a personal and/or familial history of CRC and/or CPs [29]. This evidence concerns the gene POLE and colorectal carcinoma.