OBJECTIVE: To compare the clinical behavior and outcomes of low- and high-grade endometrial stromal sarcomas (LGESS and HGESS), respectively. METHODS: Patients with endometrial stromal sarcoma from five different institutions were identified and reviewed for clinicopathologic variables, surgical management and outcomes. Statistical calculations including Chi-square, t-test and survival using the Kaplan-Meier method with the log rank test were performed. RESULTS: One hundred and five patients were identified with 72 having LGESS, 31 with HGESS and 2 having unclassified tumors. The mean age was 50 years for patients with LGESS and 64 years for those with HGESS (p<0.0001). In patients with LGESS, 68% (49 patients) had disease confined to the uterine corpus or cervix compared to 39% (12 patients) in HGESS (p=0.002). The median overall survival was 53 months for HGESS and had not yet been reached in LGESS with 87.8% alive at 80 months (p<0.0001). In HGESS patients with extrauterine disease, the presence of residual disease greater than 2 cm had a significant effect on median survival. Median survival was 52 months for those who underwent optimal cytoreduction versus 2 months for those with suboptimal residual disease (p=0.007). The impact of cytoreduction was not seen in LGESS patients with extrauterine disease with 82.1% alive at 78 months. CONCLUSIONS: Low-grade and high-grade endometrial stromal sarcomas represent two distinct clinical entities and should be treated as such. Survival in patients with high-grade tumors appears to be related to amount of residual disease at the completion of initial surgery and would suggest the need for aggressive cytoreduction. The role of surgical staging and optimal adjuvant therapy remains unclear.