BACKGROUND Incidence of extraskeletal osteosarcoma (ESOS) is extremely low and the prognosis remains unclear. We conducted this study to explore prognostic factors and the role of chemotherapy in ESOS. MATERIAL AND METHODS We screened data from the Surveillance Epidemiology and End Results (SEER) database (1975-2016). Three hundred ten patients with ESOS were included and 49.4% (107/310) of them underwent chemotherapy. We performed logistic regression analysis to investigate potential factors determining selection of chemotherapy. An inverse probability of treatment weighting (IPTW) and propensity score matching (PSM)-adjusted Kaplan-Meier curve was created and log-rank test and Cox regression analysis were performed to compare overall survival (OS) and cancer-specific survival (CSS) in patients treated with and without chemotherapy. Subgroup analysis also was conducted based on age, tumor site, stage, size, and surgery. RESULTS Chemotherapy in ESOS was not associated with improved OS in the unmatched cohort (HR, 0.764; 95% CI, 0.555-1.051; p=0.098). The insignificant treatment effect of chemotherapy was also noted in IPTW-adjusted (HR, 0.737; 95% CI, 0.533-1.021; p=0.066) and PSM-adjusted (HR, 0.804; 95% CI, 0.552-1.172; p=0.257) Cox regression analysis. The insignificant treatment effect was consistent across all subgroups and there was no significant heterogeneity of chemotherapy effect (all p for interaction >0.05). CONCLUSIONS The study suggested that chemotherapy has no significant benefit on prognosis of patients with ESOS. These findings should be considered when making treatment decisions about patients with ESOS.