In an effort to find proteins overexpressed in metastatic colonic adenocarcinomas, differential proteome analyses were undertaken using primary and metastatic tumors. Two-dimensional-gel profiles showed a number of spots that appeared in metastatic tumor in liver, but not in primary tumor. Amino acid or mass spectrometric analyses of some of these spots revealed tht they were apolipoprotein A1 (Apo A1), a protein that is normally expressed in liver and small intestine. Further RT-PCR analysis verified the expression of Apo A1 transcript in metastatic tumors and, unexpectedly, expression was also detected in the primary tumors, although the expression was weaker than in metastatic tumors. Consistent with this finding, immunohistological studies detected the weak expression of Apo A1 protein in primary colonic adenocarcinoma, in addition to the strong expression in metastatic tumors in liver and lymph nodes. In the primary tumors, expression was stronger in the deep layer than in the superficial layer, while in normal mucosal epithelial cells expression was barely visible. Further immunohistochemical study revealed that Apo A1 is expressed in some colonic adenocarcinomas of patients with no metastasis, although incidence and expression levels were lower than in carcinomas with metastases. These findings are consistent with the notion that expression of Apo A1 is associated with colonic adenocarcinoma progression, and thus Apo A1 is a potential marker of the aggression.