The presence of HER 2/neu has been reported in gastric cancer, but its impact on patient survival remains unclear. The purpose of this study was to investigate the expression of HER 2/neu in gastric cancer. A total of 218 paired resected gastric cancer and corresponding normal specimens were collected. HER 2/neu protein expression was assessed by immunohistochemical staining. The correlation between HER 2/neu expression and patient clinicopathological parameters was evaluated and the prognostic significance of HER 2/neu expression was assessed by univariate and multivariate analyses. Forty-one out of 218 (18.8%) gastric cancer specimens showed HER 2/neu-positive expression. No relationship was found between membranous HER 2/neu expression and clinicopathological parameters. However, HER 2/neu expression was correlated with poorer overall survival (p<0.001). In multivariate analysis, HER 2/neu expression was a significant independent prognostic predictor of gastric cancer (p<0.001), and was associated with poor survival in gastric cancer patients. These data indicate that HER 2/neu may play a major role in the therapeutic management of gastric cancer.