Objective: Uterine serous carcinoma (USC) is a rare highly aggressive disease. In the present study, we aimed to investigate the survival implication of the systematic lymphadenectomy in patients who underwent surgery for apparent early-stage USC. Methods: Consecutive patients with apparent early-stage USC surgically treated at six Italian referral cancer centers were analyzed. A comparison was made between patients who underwent retroperitoneal staging including at least pelvic lymphadenectomy “LND” vs.those who underwent hysterectomy alone “NO-LND”. Baseline, surgical and oncological outcomes were analyzed. Kaplan- Meier curves were calculated for disease-free survival (DFS) and disease-specific survival (DSS). Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). Results: One hundred forty patients were analyzed, 106 LND and 34 NO-LND. NO-LND group (compared to LND group) included older patients (median age, 73 vs.67 years) and with higher comorbidities (median Charlson Comorbidity Index, 6 vs. 5) (p<0.001). No differences in terms of recurrence rate (LND vs. NO-LND, 33.1% vs. 41.4%; p=0.240) were observed. At Cox regression analysis lymphadenectomy did not significantly influence DFS (HR=0.59; 95% confidence interval [CI]=0.32–1.08; p=0.09), and DSS (HR=0.14; 95% CI=0.02–1.21; multivariable analysis p=0.07). Positive node was independently associated with worse DFS (HR=6.22; 95% CI=3.08–12.60; p<0.001) and DSS (HR=5.51; 95% CI=2.31– 13.10; p<0.001), while adjuvant chemotherapy was associated with improved DFS (HR=0.38;95% CI=0.17–0.86; p=0.02) and age was independently associated with worse DSS (HR=1.07;95% CI=1.02–1.13; p<0.001). Conclusions Although lymphadenectomy did not show survival benefits in patients who underwent surgery for apparent early-stage USC, the presence of lymph node metastasis was the main adverse prognostic factors, supporting the prognostic role of the retroperitoneal staging also in this histological subtype.