In the present study, the possible involvement of homeobox-containing genes in colorectal cancer (CRC) development was investigated. Using a stepwise screening approach and RT-PCR, we have demonstrated that the human HOXB6, B8, C8 and C9 are overexpressed at various stages of CRC. In contrast, all CRC cases exhibited a marked decrease in the homeodomain-containing Cdx1 gene expression. Recent data which suggest a regulatory link between HOXB8 and several tumor suppressor genes, such as DCC, APC, and TGF beta, sustain a possible implication of homeobox genes in colon carcinogenesis. Moreover, our data showing a decrease in Cdx1 expression are consistent with the notion that genes functioning in the establishment and maintenance of the intestinal epithelium might, upon deregulation, disturb the normal control of cellular proliferation, differentiation, and death, thus leading to cancer development.