Although isolated central nervous system (CNS) relapses are rare, they may become a serious clinical problem in intensively treated patients with high-risk neuroblastoma (NBL). The aim of the study is presentation, assessment of incidence and the clinical course of isolated CNS relapses. Retrospective analysis involved 848 NBL patients treated from 2001 to 2019 at 8 centers of the Polish Pediatric Solid Tumors Study Group (PPSTSG). Group characteristics at diagnosis, treatment and patterns of relapse were analyzed. Observation was completed in December 2020. We analyzed 286 high risk patients, including 16 infants. Isolated CNS relapse, defined as presence of a tumor in brain parenchyma or leptomeningeal involvement, was found in 13 patients (4.5%, 8.4% of all relapses), all of them were stage 4 at diagnosis. Isolated CNS relapses seem to be more common in young patients with stage 4 MYCN amplified NBL, and in this group they may occur early during the first line therapy. The only or the first one symptom may be bleeding into CNS, especially in younger children, even without clear relapse picture on imaging, or the relapse may be clinically asymptomatic and found on routine screening. Although incidence of isolated CNS relapses is not statistically significantly higher in patients after immunotherapy, their occurrence should be carefully monitored, especially in intensively treated infants, with potential disruption of brain-blood barrier.