Perturbation in E-cadherin expression leads to loss of cellular adhesion with possible consequence of cellular transformation and tumor progression. The aims of this study were to determine E-cadherin expression in each subtype of gastric cancer classified by different classification systems, and to investigate the role of E-cadherin in cell differentiation, cancer invasion and metastasis. Expression of E-cadherin was analyzed in 84 patients with gastric adenocarcinoma by immunohistochemistry and correlated with clinicopahotlogical parameters. Our results showed loss of E-cadherin expression in 0% (0/3), 20.0% (9/45), 48% (15/31), 100% (3/3) and 100% (2/2) of papillary, tubular, poorly differentiated, signet-ring cell, and mucinous adenocarcinoma by Japanese histological classification. The reduction of E-cadherin expression was inversely correlated with the grade of differentiation. According to the histological classification of Lauren and Ming, the frequency of lost E-cadherin expression was higher in diffuse type (65%) and infiltrative type (64%) gastric cancer than in intestinal type (20%, P<0.001) and expanding type cancer (22%, P<0.001), respectively. The loss of E-cadherin expression was significantly associated with tumor invasion (P<0.05). Furthermore, there was a borderline association between the loss of E-cadherin expression and poor survival (P=0.109). These data demonstrated a striking correlation between E-cadherin expression and the differentiation of gastric carcinoma. The loss of E-cadherin expression may contribute to gastric cancer invasion to adjacent organs.