OBJECTIVES: Next-generation sequencing (NGS) has the potential to transform the paradigm for diagnosing and treating cancer. Widespread adoption is predicated on demonstrating the clinical utility/clinical impact of NGS and developing evidence-based reimbursement policies. A review of clinical utility, coverage and reimbursement from third-party payers was conducted in a cohort of pediatric oncology patients as part of a clinical NGS program. METHODS: NGS was performed in a CLIA-certified laboratory at Columbia University Medical Center. Testing included whole-exome sequencing (WES) of matched tumor-normal tissue, transcriptome analysis and copy number variation. WES of patient-parent DNA was performed when a constitutionally encoded disease or syndrome was suspected. Targeted sequencing of 48 or 467 cancer-associated genes was used when tumor tissue was limited. RESULTS: range, 0-89%) from commercial plans; 37% (range, 0-61%) from managed-government plans. The average reimbursement was: $3,426 (range, $750-$7,227) for WES; $837 (range, $82-$1,399) for targeted 48-gene panel sequencing; and $2,586 (range, $444-$4,149) for targeted 467-gene panel sequencing. CONCLUSIONS: NGS provided clinically-impactful information for 59% of patients but only one-third of charges for testing were reimbursed by insurers. Evidence-based reimbursement policies are needed to promote the adoption of NGS technologies that benefits patients into clinical practice.