AbstractBackgroundExtraosseous Ewing sarcoma is a rare entity and less is known about its clinical behavior and optimal treatment than for its counterpart in bone. This study is a retrospective analysis on a cohort of patients <21 years treated according to a “soft tissue sarcoma approach.”MethodsThe “extraosseous” origin of the tumor was established on radiological findings, based on the lack of any bone involvement. Patients were treated using a multimodality approach including surgery, radiotherapy, and chemotherapy. All patients received chemotherapy with alkylating agents and anthracyclines for 25 weeks (nine courses). Radiotherapy (45–54.8 Gy) was required for all cases except those who had an initial R0 resection of tumors smaller than 5 cm.ResultsFifty‐seven patients (age 2–20 years, median 14) were treated from 1990 to 2020. Ten‐year event‐free survival (EFS) and overall survival (OS) were 77.5% and 85.5% in patients with localized disease, and 11.1% and 29.6% in those with metastatic disease (p < .001) (follow‐up 5–349 months, median 107 months). In patients with localized disease, the most recent IVADo‐IVE regimen achieved excellent survivals, that is, 10‐year EFS 95.5%.ConclusionsOur study showed that satisfactory results were achieved in patients with localized extraosseous Ewing sarcoma treated with a tailored approach derived from soft tissue sarcoma protocols, which was less intensive and shorter as compared to the standards utilized for the management of bone Ewing sarcoma. Our study suggests that the extraskeletal site might be considered as a variable to stratify patients and modulate treatment intensity accordingly in Ewing sarcoma protocol.