Neuroblastoma is the most common extracranial solid tumor in children. Survival rates have improved due to advances in treatment with aggressive chemotherapy and autologous bone marrow transplantation. Usual sites of recurrence include the site of primary tumor, residual gross disease, bone, bone narrow, liver, and lungs. The authors describe a 16-month-old boy with stage IV extracerebral primary neuroblastoma who died because of an isolated central nervous system (CNS) relapse. The CNS is a rare site of relapse that is, however, increasingly diagnosed due to prolonged survival. Criteria to identify patients at increased risk of CNS relapse are urgently needed. High-risk patients should be followed-up with brain and spine magnetic resonance imaging (MRI) for timely detection of metastases and appropriate management.