Ewing sarcoma family of tumor is the second most common bone tumor in children and young adults, after osteosarcoma. Different chemotherapeutic regimens are used in treatment of relapsed/recurrent Ewing sarcoma. Promising results were achieved with combination of irinotecan and temozolomide. Our case was a 13-year-old female with relapsed Ewing sarcoma and after 12 cycles of irinotecan (20 mg/m2/10 days) and temozolomide (100mg/m2/5 days) treatment she had not any complaints, and her radiological lesions remained stable for 66 months. Irinotecan and temozolomide have been used successfully in treatment of relapsed/recurrent Ewing sarcoma, but there is a need for randomized prospective studies with larger patient groups for establishing the efficacy of this treatment protocol.