Aim: The purpose of the present study was assess the impact of next generation sequencing on the classification as well as management of primary brain tumors. Methodology: A retrospective analysis was conducted amongst 58 neuro-oncology patients who underwent NGS tumor profiling using a single commercially available platform on paraffin-embedded tissue obtained at diagnosis (20 low-grade gliomas, 12 high-grade gliomas, 11 embryonal tumors, four ependymal tumors, three meningeal tumors, and eight other CNS tumors. NGS results were analyzed for actionable mutations, variants of unknown significance and clinical impact. Results: Seventy-four percent of patients (43 of 57) had actionable mutations; 26% had only variants of uncertain significance (VUS). NGS findings impacted treatment decisions in 55% of patients; 24% were given a targeted treatment based on NGS findings. Seven of eight patients with low-grade tumors treated with targeted therapy. Turnaround time between sample shipment and report generation averaged 13.4 ± 6.4 days. Conclusion: Our experience highlights the feasibility and clinical utility of NGS in the management of neuro-oncology patients. Future prospective clinical trials using NGS are needed to establish efficacy.