Ewing sarcoma is a rare primary mesenchymal tumor of the bone that requires an intensive multimodal therapeutic approach. Multidrug chemotherapy regimens are also the backbone for relapsing/recurring Ewing sarcoma treatment, yet when relapse occurs as bone marrow infiltration, combination chemotherapy might be difficult to be administered and prognosis is poor. This report describes the case of a 22-year-old patient with Ewing sarcoma who developed severe pancytopenia due to bone marrow infiltration, who was treated with high-dose continuous infusion ifosfamide, obtaining both clinical, radiological and hematological response lasting for about 7 months.