Despite intensive chemotherapy, surgery and/or radiation, prognosis continues to be very poor in disseminated neroblastoma. Owing to neuroblastoma sensitivity progress might be achieved with high-dose radiation. Metaiodobenzyl guanidine (MIBG) coupled with 131I provides the opportunity for highly selective radiation treatment of neuroblastoma, which could potentially deliver five to 10 times the dose of conventional external-beam treatment without specific tissue toxicity. To improve the long-term results in advanced-stage neuroblastoma, we integrated this new treatment modality with conventional chemotherapy. Eight neuroblastoma patients refractory to conventional treatment were treated with 131I-MIBG-chemotherapy (vincristine, VP16, iphosphamide, carboplatin, epirubicin, cyclophosphamide) combination. Five of the eight patients responded to 131I-MIBG treatment (2 complete and 3 partial responses). There were also three patients with stable disease. Median survival was 48 months (range 1 to 84 months), and five patients relapsed in their follow-up and died of progressive disease. We concluded that a combined 131I-MIBG and chemotherapy approach is useful in advanced-stage neuroblastoma patients, with considerably less side effects. Although survival is improved when compared to conventional treatment, the overall prognosis is still poor. More lethal radionuclide conjugation to MIBG which will deliver higher tumor and lower critical organ doses may offer the best solution for targeted radionuclide therapy of neuroblastoma.