The SMAD4 gene - already identified as a candidate tumor suppressor gene for pancreatic cancers [7] located at 18q21.1 in close proximity to APC, has recently attracted considerable interest as a prime candidate target gene for the 18q deletions because of recent data linking mutations in this gene to sporadic and familial colorectal cancer [26,27]. Here, SMAD4 is linked to familial colorectal cancer.