Obesity is a well-known factor that leads to many diseases including endometrial cancer. The adipose tissue is a heterogeneous organ of internal secretion. Visfatin is a newly discovered protein produced by fat tissues. The purpose of this work was to evaluate serum level concentrations of visfatin in patients with endometrial cancer based on clinical progression and histopathological tumor differentiation. The diagnostic capabilities of visfatin protein in high differentiation (FIGO III and IV) from a lower (FIGO I and II) clinical stage and prognostic degree of cell differentiation (G1 versus G2, G2 versus G3) on the basis of the analysis of the area under the ROC curve are as follows: 0.87, 0.81, and 0.86. Significantly higher concentrations of visfatin have been observed in patients with invasion of the blood vessels (p = 0.02) and lymph node metastases (p = 0.01) in reference to the depth of infiltration of the endometrium (p = 0.004), as well as the size of the tumor (p = 0.003). Visfatin serum concentrations did not differ due to the invasion of the lymphatic vessels only. Visfatin seems to be a good marker of endometrial cancer progress. High visfatin serum level predicts poor prognosis in endometrial cancer patients.