Local control is vital for long-term survival for patients with stage III neuroblastoma, and although cure is difficult, ultimate success in stage IV neuroblastoma will necessitate control of the primary tumor as well as effective therapy of the metastases. The proper timing of surgical resection of the primary tumor is uncertain. Patients with stage III and IV neuroblastoma treated from 1977 to 1988 were retrospectively reviewed as to whether the resection was performed before or after chemotherapy. Complications assessed include significant blood loss, damage to adjacent organs, and delays before postsurgical chemotherapy could be given. Sixty patients were treated primarily at the authors' institution: 18 with stage III and 42 with stage IV disease. Chemotherapy consisted of combinations of nitrogen mustard, adriamycin, dacarbazine (DTIC), cisplatin, vincristine, and cyclophosphamide (MADDOC). Nine patients with stage III neuroblastoma underwent initial resection of the primary tumor before receiving chemotherapy. Three had complications, all with excessive blood loss (0.57, 2.0, and 3.0 times the estimated total blood volume [TBV]). One patient had renal infarction, and another had regrowth of the tumor before chemotherapy could be administered 35 days after surgery. There were no complications in the eight secondary explorations, four of which were complete resections. All had viable tumor in the resected specimen. Eleven of the 42 stage IV patients had primary resections, 5 of whom had complications: colocutaneous fistula, unilateral renal necrosis, chylothorax, and excessive blood loss (1.3 and 2 TBV). None of the 18 patients with delayed resection after 3 to 12 courses of chemotherapy had surgical complications with complete (14 patients), near complete (2 patients), or subtotal resections (2 patients). All but one patient had viable residual tumor in the resected specimen. The effect of chemotherapy on the Shimada classification of these tumors was assessed in the 17 patients (stage III and IV) for whom biopsies were available both before and after chemotherapy. Comparison of the classification before and after chemotherapy was as follows: four of nine unfavorable tumors became favorable, whereas all 8 initially favorable tumors remained unchanged. There were no statistically significant differences in overall survival based on the time of resection, regardless of stage. We conclude that surgical resection of stage III and IV neuroblastoma is safer after initial chemotherapy, but improvement in ultimate outcome for stage IV awaits better overall management. © 1991.