PURPOSE: E-cadherin, a calcium-dependent cell to cell adhesion molecule, plays a key role in the maintenance of tissue integrity. Reduction or loss of E-cadherin has been reported to have a role in the development of human malignancies. The expression of E-cadherin was analyzed in human non-small cell lung carcinoma (NSCLC) to elucidate the role in pulmonary carcinogenesis and determine the relationship with several clinicopathological factors and the prognosis. MATERIALS AND METHODS: Sixty five human cases of NSCLC were evaluated by immunohistochemical analysis for the expression of E-cadherin. The immunostaining results for E-cadherin were semiquantitatively interpreted, as preserved and reduced, in the tumor tissues. The E-cadherin expression was analyzed in relation to several clinicopathological data and the survival. The cell proliferation index of the tumors was evaluated by immunostaining with the Ki-67 antigen. RESULTS: Reduced E-cadherin expression was found in 51 cases of NSCLC tissues (78.4%) compared to that in the normal controls. Reduced E-cadherin expression was significantly correlated with male smokers and squamous cell type of the cancer, but not with histological grade, TNM stage and survival. The E-cadherin expression showed a weak inverse relationship with the proliferative activity of tumor cells, which was measured using the Ki-67 antigen. CONCLUSION: Our data support the hypothesis that reduced E-cadherin expression may play a role in the pathogenesis of human NSCLC, which might be associated with the control for cell proliferation.