SMAD4 somatic mutations have been reported in 0.8% of colon adenomas (the COSMIC database), in 0% of low- and high-grade adenomas and 0% of adenomas and intramucosal carcinomas [8, 9], indicating SMAD4 mutation is a rare event in early CRC tumorigenesis. This evidence concerns the gene SMAD4 and colorectal carcinoma.