AIM: To investigate the changes that occur in E-cadherin expression during the process of metastasis in colorectal cancer.METHODS: E-cadherin expression was detected by immunohistochemistry and two indices of expression were calculated which reflected the level of expression and the locations (membrane and cytoplasm). Univariate and multivariate survival analyses were used to assess the value of these two E-cadherin indices as predictors of both disease-free (DFS) and disease-specific (DSS)survival.RESULTS: E-cadherin membrane index (MI), but not cytoplasmic index (CI), was significantly higher in primary tumors than their metastases (P = 0.0001). Furthermore,both primary tumor MI and CI were higher among the patients who developed subsequent metastasis (P =0.022 and P = 0.007, respectively). Interestingly, both indices were higher in liver metastase compared to other anatomic sites (MI, P = 0.034 and CI, P = 0.022). The CI of the primary tumors was a significant predictor of DFS (P = 0.042, univariate analysis), with a strong inverse correlation between CI and DFS (P = 0.006, multivariate analysis). Finally, the MI of primary tumor proved to be a significant independent predictor of DSS, with higher indices being associated with a more favorable outcome (P= 0.016).CONCLUSION: Examination of E-cadherin expression and distribution in colorectal tumors can be extremely valuable in predicting disease recurrence. The observation that aberrant cytoplasmic expression of E-cadherin can predict disease recurrence is obviously of great importance for both patients and clinicians, and significantly affects decisions concing the therapy and management of the patients.