AIM: To investigate the distribution of beta-catenin in nuclei or membrane/cytoplasm of gastric carcinoma cells,the relationship between E-cadherin gene methylation and its expression, and the role of beta-catenin and E-cadherin as potential molecular markers in predicting tumor infiltration.METHODS: Twenty-nine cases of gastric carcinoma,classified as diffuse and intestinal variants, were selected for study. Nuclear and cytoplasmic proteins were purified and beta-catenin content was detected by ELISA. DNA methylation of E-cadherin/CDH1 gene promoter was studied by methylation-specific PCR and compaired with E-cadherin expression detected by immunohistochemistry.RESULTS: In 27 cases of gastric carcinoma, the ratio of beta-catenin content between nuclei and membrane/cytoplasm was correlated with the T-classification (r =0.392, P = 0.043). The significance was present between T2 and T3 groups. No correlation was detected between diffuse and intestinal variants in terms of their betacatenin distribution. In 21 cases of diffuse variants of gastric carcinoma, there was a difference in E-cadherin expression between CDH1 gene-methylated group and non-methylated group (29 % vs 71%, P = 0.027).No correlation between CDH1 gene methylation and T-classification was found, neither was the significance between E-cadherin expression and tumor infiltration grade.CONCLJSION: Comparative analysis of nuclear and membrane/cytoplasmic beta-catenin can predict local tumor infiltration. E-cadherin/CDH1 gene methylation is an important cause for its gene silence in diffuse variant gastric carcinoma. Methylation of CDH1 gene in the absence of E-cadherin is an early event in gastric carcinogenesis.