Patterns of relapse were determined for 20 high-risk neuroblastoma patients treated with chemotherapy, surgery, primary and metastatic site radiation (21 Gray), myeloablative chemotherapy, peripheral blood stem cell rescue, and 13-cis-retinoic acid. The median follow-up duration after transplant is 21 months (range, 8-34 months). The event-free survival and overall survival at 2 years were 45 and 75%, respectively. There were 2 primary site recurrences. Metastatic sites that became MIBG-scan negative on induction chemotherapy were not irradiated. Four patients relapsed in irradiated metastatic sites, 3 in the skull, 1 in the liver. Failure also occurred at 2 skull sites treated with chemotherapy only, and at 5 new sites: 1 skull, 2 distant lymph nodes, and 2 bones other than skull. Eight of 20 patients had skull metastasis at presentation; 6 were irradiated and 3 were controlled. Skull metastasis warrants more aggressive evaluation and treatment.