Transforming growth factor (TGF) β mediates a tumor suppressor pathway in human colon epithelial cells. We were interested in identifying and characterizing novel genes regulated by the TGFβ pathway in the colon. We employed expression microarrays to identify transcripts induced by TGFβ in Vaco 330, a colon adenoma cell line. We then used expression microarrays to determine which of these TGFβ induced transcripts are down-regulated in metastatic colon cancer. Northern analysis and real-time reverse transcription PCR confirmed and quantified our findings from the microarrays. These analyses highlighted C8orf4 as induced by TGFβ in colon cells. Moreover, C8orf4 is expressed in most normal colon mucosa samples, and is not expressed in most colon cancer metastases or colon cancer cell lines. Colon cancer primary tumors showed reduced expression of C8orf4 relative to normal mucosa, possibly reflecting contributions of C8orf4 expression in stromal cells. C8orf4 is a gene regulated by TGFβ signaling and loss in advanced colon cancer suggests C8orf4 may play a role in colon cell differentiation or growth regulation. © 2004 Wiley-Liss, Inc.