Decreased expression of VDUP1, which is an interesting stress response gene, has been shown in rat mammary tumors and has been discussed in relation to the development of the tumor. However, VDUP1 expression in clinical specimens of human cancer remains unclear. We employed TaqMan RT-PCR assay to investigate VDUP1 expression in surgical specimens of primary tumors and their adjacent normal tissues from gastrointestinal cancer patients, 40 with colorectal and 12 with gastric cancers. TaqMan RT-PCR assay showed that VDUP1 expression in colorectal and gastric cancers was significantly lower than that in their adjacent normal tissues (p < 0.0001 and p < 0.001, respectively). In addition, we found that VDUP1 expression was associated with clinical stage in colorectal cancer (p < 0.01). VDUP1 expression in stage II patients was significantly higher than that in stage III (p < 0.05) and in stage IV patients (p < 0.01). These results suggest a possible role of VDUP1 in the pathogenesis of gastrointestinal cancer, as well as its clinical significance.