SMAD4 and colorectal cancer: Colorectal cancer (CRC) is the third most common type of non-skin cancer worldwide and the third cause of cancer-related death in the Western world.1,2 The molecular defects in CRC can be due to changes that result in increased activity of oncogenes or to changes that lead to loss of function of the tumor-suppressor genes.3 A large number of colorectal tumors show mutations in the KRAS oncogene as well as in the APC, p53, and SMAD4/DPC4 tumor-suppressor genes.