Liver-intestine (LI) cadherin represents a novel type of cadherin within the cadherin superfamily, and is distinguished from other cadherins by specific structural and functional features. Among normal tissues, LI-cadherin is known to be expressed in the intestinal mucosa, while its expression in cancerous tissue has not been investigated to date, except in gastric carcinoma. In the present study we investigated LI-cadherin expression immunohistochemically using our newly established monoclonal antibody in a large set (n = 102) of tumor specimens from patients with ductal adenocarcinoma of the pancreas, and correlated the findings with the patients' survival. LI-cadherin expression was seen focally in normal pancreatic ducts. In carcinoma, well-differentiated carcinoma cases strongly expressed LI-cadherin, whereas less differentiated areas and poorly differentiated carcinoma cases expressed less or were negative. Kaplan-Meier analysis for all patients demonstrated that high LI-cadherin expression (>25% of cells stained positive) correlated with good survival (P < 0.001). Cox regression analyses demonstrated that LI-cadherin expression was one of the strongest predictors of outcome, independent of all other variables, and low LI-cadherin expression correlated with tumor de-differentiation and advanced stage. Furthermore, galectin-3 was identified as being coimmunoprecipitated with LI-cadherin and this interaction was inhibited by lactose in a dose-dependent manner, but not by sucrose. Because galectin-3 has been observed to show a similar expression pattern to LI-cadherin in ductal adenocarcinoma of the pancreas, expression of LI-cadherin and this interaction could have some role in ductal adenocarcinoma of the pancreas.