The ultramutated colorectal carcinomas had an extremely high mutation rate with a characteristic nucleotide base change spectrum with increased C-to-A transversions, resulting from the presence of a mutation that inactivates the proofreading function within the exonuclease domain of the polymerase E (POLE) DNA replicating enzyme, or rarely of POLD1. This evidence concerns the gene POLE and colorectal carcinoma.