Background: The optimal type and intensity of CHT in the treatment of STET is still a matter of debate. The CWS group has treated STET similar to rhabdomyosarcoma. We have analyzed the prognosis of STET in relation to the CHT regimens used in three consecutive CWS studies CWS-91, -96 and CWS- 2002P. Methods: 243 pts with localized STET were included. Their median age was 12 (range 0.1-29) yrs. In the CWS-91 pts with primary tumor resection (IRSG I and II) were treated with VACA (vincristine (VCR), actinomycin D (Act D), cyclophosphamide (CYC), doxorubicin (DOX), for 10 or 20 weeks. All other CWS-91 pts (high risk group, HRG) received EVAIA (ifosfamide (IFO) instead of CYC plus VP16) for 37 weeks. In the CWS-96 and CWS-2002P all STET pts were allocated to the HRG. In CWS-96 therapy was randomized: VAIA (IFO, DOX, Act D, VCR) vs. CEVAIE (Epi-DOX instead of DOX, plus carboplatin and VP16), for 25 weeks. In CWS-2002P VAIA (25 weeks) plus maintenance CHT with CYC and vinblastine (VBL) for 26 weeks were used. The cumulative doses varied: IFO 24-72 g/m², CYC 4.8-7.35 g/m², DOX 120-360 mg/m², Act D 3-9 mg/m², VP16 1.8-5.4 g/m². Irradiation was stratified depending on results of the primary or secondary resection and response. Results: 5 yr event free (EFS) and overall survival (OS) were 64% and 73%. The median observation time of survivors was 9 yrs. 5yr EFS and OS by study were: CWS-91 64 % and 72 %, CWS-96 57% and 70 %, CWS-2002P 78 % and 86 % respectively (n.s.). 5 yr EFS and OS for VACA arm were 79% and 90%. 5 yr EFS and OS by CHT for HRG were: EVAIA 57% and 65%, VAIA 64% and 80%, CEVAIE 45% and 54%, VAIA with CYC/VBL 84% and 87%, respectively (p = 0 .003). 5yr EFS and OS for irradiated (n = 181) vs. not irradiated (n = 48) patients were 63 % and 72% vs. 63% and 79%, respectively. Conclusions: The outcomes between CHT arms differed significantly: CEVAIA correlated with the worst outcome while VAIA with CYC/VBL showed the best results. A small group of low risk patients have an excellent prognosis with substantially reduced CHT. Ewing tumors are biologically heterogeneous and more diversification in therapy stratification is warranted to avoid overtreatment.