Traditional therapy for malignant primitive neuroectodermal tumors in children includes surgery, multi-agent chemotherapy, and radiation. Given the poor prognosis with conventional therapy alone, newer treatment approaches have incorporated high-dose chemotherapy followed by autologous stem cell rescue. Treatment with chemotherapy and radiation is not without unanticipated and unwanted side effects. Specifically, radiation-induced damage to the central nervous system can occur, though the frequency is thought to be acceptably low. This report describes two cases of treatment-related transverse myelitis in patients who received induction chemotherapy and craniospinal irradiation followed by high-dose chemotherapy with autologous stem cell rescue. Other patients treated with a similar strategy but different sequence and timing of treatment did not experience symptoms of myelitis, suggesting that the specific timing of radiation in relationship to the chemotherapy may be of critical importance.