BACKGROUND: Neuroblastoma in older children and adolescents has a distinctive, indolent phenotype, but little is known about the clinical and biological characteristics that distinguish this rare subgroup. Our goal was to determine if an optimal age cut-off exists that defines indolent disease and if accepted prognostic factors and treatment approaches are applicable to older children. PROCEDURE: Using data from the International Neuroblastoma Risk Group, among patients >/=18 months old (n = 4,027), monthly age cut-offs were tested to determine the effect of age on survival. The prognostic effect of baseline characteristics and autologous hematopoietic cell transplant (AHCT) for advanced disease was assessed within two age cohorts; >/=5 to <10 years (n = 730) and >/=10 years (n = 200). RESULTS: Older age was prognostic of poor survival, with outcome gradually worsening with increasing age at diagnosis, without statistical evidence for an optimal age cut-off beyond 18 months. Among patients >/=5 years, factors significantly prognostic of lower event-free survival (EFS) and overall survival (OS) in multivariable analyses were INSS stage 4, MYCN amplification and unfavorable INPC histology classification. Among stage 4 patients, AHCT provided a significant EFS and OS benefit. Following relapse, patients in both older cohorts had prolonged OS compared to those >/=18 months to <5 years (P < 0.0001). CONCLUSIONS: Despite indolent disease and infrequent MYCN amplification, older children with advanced disease have poor survival, without evidence for a specific age cut-off. Our data suggest that AHCT may provide a survival benefit in older children with advanced disease. Novel therapeutic approaches are required to more effectively treat these patients.