Objective. Endometrial cancer is one of the most common malignancies in the world. There is no effective screening method used for predicting the clinical stage of the disease in the preoperative period and to plan the surgical procedure. The aim of this study is to compare the serum levels of CA-125 and HE-4 with MRI, to evaluate their ability to predict the depth of myometrial invasion in patients diagnosed with endometrial cancer, and to compare the specificity between these two tests. Materials and Methods. This prospective study was conducted at Dokuz Eylul University Faculty of Medicine, Department of Obstetrics and Gynecology, between February 2019 and February 2020. A total of 47 cases were included in the study. The cases were evaluated with MRI preoperatively to determine the extent of the disease. Preoperative serum CA-125 and HE-4 levels were measured by ELISA method and compared, and the superiority of the tests to each other in determining the depth of myometrial invasion was evaluated. Results. In patients with endometrioid cancer, preoperative CA-125 and HE-4 levels were found to be higher if the myometrial invasion is >50% and lymphovascular space invasion is positive, and the difference was statistically significant. A cut-off of 7,05 U/ml for CA-125 could detect the deeper myometrial invasion with a sensitivity of 83% and a specificity of 52%, respectively. A cut-off of 94,25 pmol/L for HE-4 could detect deeper myometrial invasion with a sensitivity of 75% and a specificity of 56%, respectively. The sensitivity of MRI in determining the depth of myometrial invasion was 87,1%, and the specificity was 86,7%. Conclusions. MRI, HE-4 and CA-125 were found to be valuable tests in predicting the extent of the disease and planning the surgical treatment. All three methods successfully predicted the myometrial invasion depth of the disease. The success rates of the tests in predicting the depth of myometrial invasion were MRI, HE-4 and CA-125, respectively. HE-4 and CA-125 could not reach the sensitivity and specificity of MRI in determining the depth of myometrial invasion at any cut-off value. However, it was proved in this study that they can play important roles as simpler and more cost-effective tests in determining the extent of the disease, able to contribute to surgical planning during preoperative evaluation.