Failure of apoptosis is one of the hallmarks of cancer. As an adaptor, FADD plays a crucial role during death receptor-mediated apoptosis. We previously reported that the FADD gene is somatically mutated in non-small cell lung cancers. To explore the possibility that the genetic alterations of the FADD gene might be involved in the development of other human cancers, we analyzed the entire coding region and all splice sites of the human FADD gene to detect somatic mutations in 116 stomach cancers and 98 colon cancers. Overall, we detected a somatic missense mutation of the FADD gene in a colon carcinoma, which was predicted to change an amino acid (R140H) in the death domain (DD) of the FADD protein. This is the first report of FADD gene mutation in gastrointestinal cancers, and our data suggest that the FADD gene is rarely mutated in human colon and stomach cancers.