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Serum markers with increased sensitivity and specificity for endometrial cancer are required. To date, no good marker has met this standard. The aims of our study were to evaluate the utility of tumor markers HE4, CA125, CA724, and CA19-9 as potential markers in patients diagnosed with endometrial cancer.Blood samples from 105 patients with endometrial cancer and 87 healthy women were analyzed by Roche electrochemiluminescent immunoassay, and serum values were measured for the following biomarkers: HE4, CA125, CA724, and CA19-9.Serum HE4, CA125, CA724, and CA19-9 concentrations were significantly higher in patients with endometrial cancer, compared with controls (P < .001). In the receiver operating characteristic analysis, the area under the curve value for combination of HE4, CA125, CA724, and CA19-9 was 82.1% (95% confidence interval: 75.3%-86.2%), the maximum area of the test groups. For all stages of patients with endometrial cancer, HE4 had higher sensitivity (58%), positive predictive value (60%), and negative predictive value (67%) than any other single tumor marker, and in the combination of HE4, CA125, CA724, and CA19-9, the sensitivity and positive predictive values reached 59.1% and 88%, respectively. Meanwhile, the receiver operating characteristic area under the curve of the combination of the 4 markers was significantly increased than any other group, either in stage I or in stage II to IV cases. HE4 and CA125 both correlate with advanced age; in addition, HE4 was related to pathology subtypes and positive adnexal involvement, CA125 was related to International Federation of Gynecology and Obstetrics stage, CA19-9 was related to International Federation of Gynecology and Obstetrics stage, and CA724 was correlated with positive lymph node.Combination of HE4, CA125, CA724, and CA19-9 has the highest value in diagnosing endometrial cancer, and they can be a useful tissue immune marker for patients with endometrial cancer.