AIM: To investigate the changing pattern of α-catenin expression and its relationship to clinical and pathological features of colorectal cancer (CRC) patients. METHODS: Archival tumor samples were analyzed using immunohistochemistry (IHC) for α-catenin in 91 patients with advanced CRC. RESULTS: The values of α-catenin membrane index (MI) and cytoplasmic index (CI) were significantly related to the depth of tumor invasion (P = 0.027, P = 0.020, respectively), high indices being associated with increased depth of the primary tumor invasion (T3 and T4). Similarly, patients with high α-catenin expression had a signifi cantly increased risk of lymph node metastasis (32/39 vs 37/52 for MI and 37/45 vs 32/46 for CI) (P = 0.001, P = 0.0001, respectively, for LNN status). An altered expression (i.e., cytoplasmic pattern) was also related (P = 0.047) to the response to chemotherapy; patients with low CI were more responsive (CR: 7/46) than patients with high CI values (CR: 0/45). There was a marginal effect on survival in patients time with metastases (SWM) (P = 0.087); patients with low CI showing slightly longerSWM, but no such effect on disease free survival (DFS) or disease specifi c survival (DSS). As to co-expression with another member of the adhesion complex (β-catenin), high α-catenin/β-catenin MI index was of marginal signifi cance in predicting longer DSS (P = 0.063, log-rank). CONCLUSION: The results implicate that high α-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in CRC. METHODS: Archival tumor samples were analyzed using immunohistochemistry (IHC) for α-catenin in 91 patients with advanced CRC . RESULTS: The values ​​of α-catenin membrane index (MI) and cytoplasmic index (CI) were significantly related to the depth of tumor invasion (P = 0.027, P = 0.020, respectively) Similarly, patients with high α-catenin expression had a signifi cantly increased risk of lymph node metastasis (32/39 vs 37/52 for MI and 37/45 vs 32/46 for CI) ( P = 0.001, P = 0.0001, respectively, for LNN status). An altered expression (ie, cytoplasmic pattern) was also related (P = 0.047) to the response to chemotherapy; patients with low CI were more responsive 46) than patients with high CI values ​​(CR: 0/45). There was a marginal effect on survival in patients with metastases (SWM) (P = 0.087); patients with low CI showing slightly longer SWDM, but no such effect on disease free survival (DFS) or disease specifi c survival -expression with another member of the adhesion complex (β-catenin), high α-catenin / β-catenin MI index was of marginal signifi cance in predicting longer DSS (P = 0.063, log- rank). CONCLUSION: The results implicate that high alpha-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in CRC.