Early diagnosis of Gastric adenocarcinoma could increase survival of the patients and also remarkably reduce treatment costs. This study aimed at evaluating the diagnostic value of serum P35 in comparison with tissue P35 in gastric adenocarcinoma and their relationship with microscopic prognostic factors. In this descriptive analytical study, 35 patients (74.3% male and 25.7% female with mean age of 63.00 +/- 12.75 years with gastric adenocarcinoma were evaluated. Blood samples were taken from all patients before gastrectomy to evaluate serum P35 with ELISA method and after surgery tissue samples were gathered to evaluate tissue P35 with immunohistochemical method. The relation between tissue and serum P35 with severity of the disease and microscopic findings was assessed. Tissue P35 was negative in 57.1%, positive in 22.9% and very positive in 20%. Mean serum P35 was 1.34 +/- 0.43 mg dL(-1). There was no relation between serum P35 and adenocarcinoma type, tumor grade, vascular and neurological invasion and number of lymph node involved. Serum P35 levels significantly increased by increase in tissue P35 positivity (p = 0.004). There was significant correlation between tissue P35 and adenocarcinoma type (p = 0.006), neurological involvement (p = 0.04) and number of involved lymph nodes (p = 0.001). Although serum P35 level was higher in cases with more lymph node involvement and vascular and neural invasion, the marker was not capable to predict the involvement degree of stomach cancer. In comparison with serum P35, tissue P35 plays more significant role in these cases.