BACKGROUND To examine whether the combined detection of serum tumor markers (CEA, CA72-4, CA19-9, CA15-3 and CA12-5) improves the sensitivity and accuracy in the diagnosis of gastric cancer (GC). MATERIALS AND METHODS An automatic chemiluminescence immune analyzer with matched kits was used to determine the levels of serum CEA, CA72-4, CA19-9, CA15-3, and CA12-5 in 87 patients with gastric cancer (GC group), 60 patients with gastric benign diseases (GBD group) who were hospitalized during the same period, and 40 healthy subjects undergoing a physical examination. The values of these 5 tumor markers in the diagnosis of gastric cancer were analyzed. RESULTS The levels of serum CEA, CA72-4, CA19-9, and CA12-5 were higher in the GC group than in the GBD group and healthy subjects, and these differences were significant (P<0.001). Although the level of CA15-3 was higher than those of benign lesion and healthy control groups, the difference was not statistically significant (P>0.05). The combined detection of CEA, CA72-4, CA19-9, and CA12-5 had a higher diagnostic value for gastric cancer than did single detection, and the positive detection rate of the combined detection of the four tumor markers was 60.9%. The diagnostic power when using the combined detection of CA72-4, CEA, CA19-9, and CA12-5 was the best. CONCLUSIONS The combined detection of serum CA72-4, CEA, CA19-9 and CA12-5 increases the sensitivity and accuracy in the diagnosis of GC and can thus be considered an important tool for early diagnosis.