Liver-intestine cadherin (LI-cadherin) is a recently identified member of the cadherin superfamily. We examined LI-cadherin expression in four human colorectal carcinoma cell lines and 45 human primary colorectal carcinomas using a monoclonal antibody against LI-cadherin. We also investigated the correlation between LI-cadherin expression and clinicopathologic parameters. Among the cell lines, LI-cadherin expression was detected in a differentiated phenotype, but not in dedifferentiated phenotypes. Among the 45 tumor samples, LI-cadherin expression was preserved in 28 (62%) and reduced in 17 (38%). Reduced LI-cadherin expression was significantly associated with a high tumor grade (P = 0.015), lymphatic invasion (P = 0.033), lymph node metastasis (P = 0.015), and an advanced pTNM stage (P = 0.033). These results suggest that analysis of LI-cadherin expression may help to indicate the biological aggressiveness of this malignancy.