Data from patients with localized and stage 4S neuroblastoma were analyzed to define a new, extended low-risk group that does not require postoperative chemotherapy. Nine hundred eight patients with stage 1 to 3 and 4S disease without MYCN amplification were included. The prognostic impacts of age, stage, serum lactate dehydrogenase (LDH) activity, histology, and alterations of chromosomes 1p, 11q, and 3p were analyzed. By univariate analysis, alterations of chromosomes 1p and 11q were correlated with poor event-free survival (EFS) and overall survival (OS). Chromosome 3p alterations were prognostic only for EFS. Age, stage, and histology were found prognostic for EFS and OS. Stage 3 patients older than 2 years showed the worst outcome and were excluded from multivariate analysis. By multivariate analysis, status of 1p (P = 0.005, hazard ratio [HR] 3.6) and 11q (P = 0.024, HR 2.8) proved prognostic for EFS but only 1p status (P = 0.009, HR 3.0) for OS. The new low-risk group was defined as no MYCN amplification and either stage 1, stage 2 without 1p alterations, stage 3 two years of age or younger without 1p alteration, or stage 4S. These patients had a better outcome (3-year EFS 88.0 +/- 1.3%, 3-year OS 97.4 +/- 0.6%) than stage 2 and 3 patients with 1p alterations and stage 3 patients older than 2 years (3-year EFS 51.7 +/- 6.5%, P < 0.001; 3-year OS 83.4 +/- 4.5%; P < 0.001). The authors conclude that postoperative chemotherapy is required only in a small group of patients with localized and stage 4S disease without MYCN amplification.