Endometrial cancer is the most common genital cancer in high‐resource countries. Treatment is essentially surgical, but the role of lymphadenectomy in the treatment of low‐stage and low‐grade tumors has not been defined. Although no tumor factors have been validated for use as preoperative prognostic markers of endometrial cancer at yet, human epididymis protein 4 (HE4) has received much interest as a potential diagnostic and prognostic tumor marker. Since 2008, several studies have explored its utility in the management of endometrial cancer: HE4 may be a useful preoperative prognostic marker because it is associated with lymphatic metastasis and other unfavorable factors in endometrial cancer. In addition, some studies have explored a HE4 cutoff value to classify patients according to lymph node involvement. HE4 might be beneficial as a serum marker that helps clinicians in the decision‐making algorithm for treatment of endometrial cancer, enabling them to perform individualized operations and decrease the adverse effects of unnecessary surgery.