Data on treatment outcome of adult patients with Ewing's sarcoma family of tumors (ESFT) are scarce. In some reports, adults with ESFT were found to have a worse outcome than children. The aim of this study was to assess compliance with chemotherapy protocols and toxicity and to compare two adult age groups. A retrospective analysis of clinical records of adult patients (≥ 21 years) treated at our center for ESFT from January 2000 to June 2010 was performed. Data recorded included demographics, clinical features, and outcomes. Patients were divided into two groups: ≥ 40 years (Group A) and < 40 years (Group B). Twenty-two patients were included in the analysis, nine in Group A and 13 in Group B. Median age was 54 years in group A and 29 years in group B. Extra-osseous origin was diagnosed in 8/9 (89%) patients in group A and 8/13 (61%) patients in group B (P = 0.3). No significant differences between the two age groups regarding dose intensity, compliance with protocol, hematological and non-hematological toxicity, or overall survival were found. It was concluded that a multidisciplinary approach including multi-agent chemotherapy for a prolonged period of time is appropriate in adult patients with ESFT. Dose intensity of chemotherapy should be determined according to the patient's clinical status and comorbidities. Treatment protocols used in the pediatric population, including high-dose chemotherapy, should be adapted for the adult population.