Interaction of MUC1 with beta-catenin plays a significant role in tumor progression and invasion. However, the clinical significance of coexpression of MUC1 and subcellular beta-catenin expression in colorectal carcinoma remains unclear. The present study evaluated the clinicopathological significance of their combined expression for predicting prognosis. Seventy-seven colorectal carcinomas were subjected to immunohistochemical staining with anti-MUC1 KL-6 mucin and anti-beta-catenin monoclonal antibody. Positive KL-6 mucin expression was correlated with decreased membranous beta-catenin expression (P=0.022), while no correlation was found between positive KL-6 expression and nuclear beta-catenin expression (P=0.142). Preservation of membranous beta-catenin expression was detected in 35 cases (45.5%) and decreased membranous beta-catenin expression was found in 42 cases (54.5%). Negative KL-6 expression was detected in 31 cases (41.3%) and positive expression was seen in 46 cases (59.7%). Combined positive KL-6 expression and decreased membranous beta-catenin expression was found in 30 patients (39.0%), whose survival was significantly worse than that of patients with other expression patterns for these two molecules (53.3 vs. 84.4%, P=0.005). Multivariate analysis showed that this combination was as an independent predictor of survival. We concluded that the combined pattern of positive KL-6 expression and decreased membranous beta-catenin expression by colorectal carcinoma is a useful biomarker for distinguishing a subgroup of patients with a worse prognosis.