Hepatocyte growth factor activator inhibitor type 2 (HAI-2) was recently identified as a potent inhibitor of hepatocyte growth factor activator. It was also independently reported as placental bikunin (PB) and as a protein over-expressed in pancreatic cancer. The expression of HAI-2/PB was analyzed in human normal colon mucosa, adenomas, and carcinomas. HAI-2/PB mRNA was consistently expressed in the colorectal mucosa. The expression was conserved in the neoplastic colorectal mucosa, and no relationship was found between HAI-2/PB mRNA levels and tumor stages. Moreover, 13 out of 14 colorectal carcinoma cell lines expressed HAI-2/PB mRNA. Immunohistochemically, HAI-2/PB proteins were predominantly stained beneath the apical surface of normal enterocytes. In tumor tissues, rather disarranged intracytoplasmic granular staining was observed. The HAI-2/PB immunoreactivity was well conserved in the colonic adenoma-carcinoma sequence, and this protein may have important unknown function in the intestinal mucosa.