HER2/neu is one of the few identified oncogenes in tumorigenesis Attention has been focused on the potential effect of HER2/neu mutations in the tyrosine kinase domain on carcinoma-targeted therapy However, data concerning HER2/neu mutations in Chinese patients with gastric cancer (GC) are limited This study aimed to detect the expression and somatic mutations of HER2/neu in Chinese patients with GC Immunohistochemical staining for HER2/neu was performed on 72 formalin-fixed, paraffin-embedded specimens of GC (40 intestinal and 32 diffuse type) The correlation between the overexpression of HER2/neu and clinicopathological parameters was statistically analyzed Somatic mutations in the tyrosine kinase domain of HER2/neu in the 72 patients were detected by direct sequencing In the GC group, overexpression of HER2/neu was detected in 13 of the 72 GC patients and in 4 of the 72 adjacent tissues in the non-tumorous group (18 1 vs 5 6%, P < 0 05) Furthermore, the intestinal type of GC exhibited a higher rate of HER2/neu overexpression than the diffuse type (29 7 vs 57%, P < 0 05) The rate of HER2/neu overexpression in stage III-IV (TNM stage) GC cases was significantly higher than that in stage I-II (28 2 vs 6 6%, P < 0 05) HER2/neu overexpression correlated with a significantly less favorable patient survival (P=0 046) No somatic mutations in the tyrosine kinase domain of HER2/neu were detected in tumor tissues or the corresponding non-tumorous ones in the specimens obtained from the 72 Chinese GC patients Results suggest that overexpression of HER2/neu is a frequent molecular event strongly associated with a poor patient prognosis, whereas the incidence of somatic mutations of the HER2/neu kinase domain is more likely a low-frequency event in Chinese GC patients