Neuroblastoma is an embryonal tumor of the sympathetic nervous system and the most common extracranial tumor of childhood. By sequencing transcriptomes of low- and high-risk neuroblastomas, we detected differentially expressed annotated and nonannotated long noncoding RNAs (lncRNAs). We identified a lncRNA neuroblastoma associated transcript-1 (NBAT-1) as a biomarker significantly predicting clinical outcome of neuroblastoma. CpG methylation and a high-risk neuroblastoma associated SNP on chromosome 6p22 functionally contribute to NBAT-1 differential expression. Loss of NBAT-1 increases cellular proliferation and invasion. It controls these processes via epigenetic silencing of target genes. NBAT-1 loss affects neuronal differentiation through activation of the neuronal-specific transcription factor NRSF/REST. Thus, loss of NBAT-1 contributes to aggressive neuroblastoma by increasing proliferation and impairing differentiation of neuronal precursors. Display omitted •Characterization of long noncoding RNA transcriptome of neuroblastoma tumors•NBAT-1 is a biomarker for predicting the clinical outcome of the neuroblastomas•NBAT-1 epigenetically regulates cell proliferation and migration pathways•NBAT-1 is required for neuronal lineage commitment Pandey et al. identify the long noncoding RNA NBAT-1 as a prognostic biomarker in neuroblastoma through transcriptome sequencing. NBAT-1 loss increases proliferation and impairs differentiation of neuronal precursors leading to more aggressive disease.