To determine whether expression of the tumor suppressors p16 and Rb is altered in gastric carcinoma. Mucosal biopsies were endoscopically obtained from patients with superficial gastritis (n = 12), atrophic gastritis (n = 15), atypical hyperplasia (n = 20) and gastric cancer (n = 40). Upon obtainment, all samples were immediately fixed with 10% buffered formalin, embedded in paraffin, and sectioned serially. Protein expression of p16 and Rb was detected by immunohistochemistry (ABC method). The gastric epithelium samples showed various degrees of nuclear immunostaining for p16 and Rb according to the different stage of lesion. Progressive pathology of the lesions was associated with a decreasing trend in positive immunostaining for p16 protein (83.3% > 73.3% > 30.0% > 27.5%) but an increasing trend for Rb protein (25.0% > 46.7% > 60.0% > 67.5%). A negative correlation was found between these two parameters and gastric cancer. Correlation analysis of the 40 cases of gastric cancer identified a negative correlation for 20 of the cases. When positive (n = 9) and negative tissues (n = 11) were compared, a statistically significant difference was found (50.0%, 22.5%, 27.5%) (P < 0.05). Abnormal expression of p16 and Rb may play an important role in gastric carcinogenesis.