Abstract Introduction: Beta-catenin is a member of a cadherin-catenin complex mediating cell adhesion. It is also a key protein of Wnt/Beta-catenin pathway responsible for cell cycle and proliferation. This is important for initiation and progression of colorectal cancer. The aim of this study was to determine expression and localization of E-cadherin, Beta-catenin and Wnt-1 proteins in colorectal tumors. Description: Forty-four unrelated patients with advanced colorectal carcinoma (CRC) were enrolled consecutively from CRC patients attending palliative care. Expression of Beta-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on formalin-fixed, paraffin-embedded primary colorectal tissue. The expression was scored by two independent observers who had no knowledge of the clinical data. Correlation was measured with Spearman test, overall survival were analyzed with Kaplan-Meier method. Log-rank test was used for univariate analysis, while Cox regression model for multivariate analysis. A value of p < 0,05 was considered significant. Results: Decreased expression of membrane E-cadherin and Beta-catenin was observed in 34% and 27% of patients, respectively. Abnormal cytoplasmic E-cadherin was detected in 32% of cases and abnormal cytoplasmic and nuclear Beta-catenin was detected in 50% and 25% of patients, respectively. 60% of patients had decreased cytoplasmic Wnt-1 expression. Correlation was seen between cytoplasmic E-cadherin and cytoplasmic Beta-catenin (R 0,35; p=0,019). Nuclear localization of Betacatenin was correlated with localization of primary tumor (the highest expression in rectum) (R 0,48; p=0,001) and tumor size (R 0,32; p=0,035). Lower Wnt-1 expression was correlated with higher nodal stage (R -0,31; p=0,047). Nuclear Beta-catenin was an adverse prognostic factor in univariate analysis (log-rank test p=0,034) which was confirmed in multivariate analysis (HR 4,27 95% CI 1,70–10,72; p=0,002). Higher CEA serum level before treatment (HR 4,30 95% CI 1,35–13,66; p=0,013) and female sex (HR 2,75 95% CI 1,24–6,10; p=0,013) were also independent prognostic factors. Conclusions: This finding supports that Beta-catenin is an independent prognostic factor for colorectal carcinoma. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B33.