Endometrial cancer is becoming an increasing problem. Taking into account its pathomechanisms, we aimed to investigate whether FGF 21, an important metabolism regulator, could be used as a biomarker for endometrial cancer. The study included 233 patients who were classified into five subgroups depending on the result of the histological examination: endometrial carcinomas, sarcomas, endometrial polyps, fibroids, and normal endometrium. Statistically significantly higher FGF 21 levels were found in patients diagnosed with malignant lesions (p p = 0.020) and the presence of lymph node metastases (p = 0.009). The diagnostic performance characteristics of FGF 21 as an EC diagnostic marker demonstrated an AUC of 0.677. Of all of the assessed biomarkers, FGF 21 had the highest specificity (90%), yet limited sensitivity (41%). Additionally, HE4 and CA 125 were confirmed to have roles as EC biomarkers, with a higher accuracy for HE4 (79% vs. 72%).