Although most patients diagnosed with extranodal NK/T-cell lymphoma (NTCL) have localized disease, radiotherapy alone is unsatisfactory because of frequent systemic failure and conventional doxorubicin-based chemotherapy has low efficacy. Twenty-six patients with NTCL received ifosfamide, methotrexate, etoposide and prednisolone (IMEP) chemotherapy as first-line treatment [ifosfamide 1.5 g/m2 (days 1 - 3), methotrexate 30 mg/m2 (days 3 and 10), etoposide 100 mg/m2 (days 1 - 3) and prednisolone 120 mg (days 1 - 5)]. Radiotherapy was administered only to patients with Ann Arbor stage I/II that had not achieved complete remission (CR) or to those that developed local failure after completing chemotherapy. Sixteen patients (group A) had nasal or upper aerodigestive tract localization (stage I/II) and 10 (group B) had extranasal or disseminated disease. Of the 14 evaluable patients in group A, 11 (79%) achieved CR after IMEP alone and 13 (93%) after chemotherapy +/- additional radiotherapy. Although, out of the 11 patients who achieved CR with chemotherapy alone, seven developed recurrence, all recurrences were local failure and successfully treated by additional curative radiotherapy. However, patients in group B responded poorly (CR 13%). IMEP regimen was active in NTCL patients with nasal or upper aerodigestive tract localization. Considering local failure rate after IMEP alone, initial IMEP chemotherapy followed by radiotherapy may be a promising treatment strategy in this subset of NTCL.