Objective: to study the diagnostic sensitivity of human epididymis protein 4 (HE4) as compared and in combination with CA125 in endometrial cancer (EC). Material and methods. Serum CA125 and HE4 levels were estimated in 172 patients with verified EC (endometrioid adenocarcinoma) on an ARCHITECT analyzer («Abbott Diagnostics», USA), by applying ARCHITECT СА125 assay and ARCHITECT HE4 assay kits, respectively. The discriminative level (DL) of CA125 was 35 U/ml. The HE4 DLs of 70.0 and 120.0 pmole/l were used for patients aged ≤55 and >55 years, respectively. Results. There was evidence suggesting the rather low and similar values of the diagnostic sensitivity of the examined markers that averaged 31.6% for HE4 and 29.5% for CA125 at all stages of this disease. The stage sensitivity of HE4 was 8.3% in pT1, 36.4% in pT2, and 50.0% in pT3 and that of CA125 was 9.7, 45.5, and 33.3%, respectively. The markers proved to be complementary to each other. Owing to this, determination of their combination (by considering the increase of at least one marker in the pair to be a positive episode) enhanced the sensitivity of the specifying laboratory diagnosis of EC up to 44.0% and there was an obvious stage-dependence: 15.3% in pT1, 50% in pT2, and 66.7% in pT3. Conclusion. There is evidence that it is expedient to assess the pair of markers CA125 and HE4 in patients with a disseminated tumor process, which need to be monitored for the evaluation of the efficiency of treatment and preclinical detection of recurrent EC.