Background: Although well characterized in pilocytic astrocytoma and pleomorphic xanthroastrocytoma, the prevalence of BRAF alterations in glioblastoma (GBM) and astrocytoma is not well established. Characterization of BRAF mutations in glioblastoma and astrocytoma may identify a subgroup of patients with sensitivity to BRAF inhibitors. Methods: DNA was extracted from 95 diffuse gliomas (grade II-IV) at our institution and an independent set of 714 gliomas, and was subjected to hybrid capture for 315 or 265 cancer-related genes plus select intronic regions. Sequencing was performed to a mean coverage depth of > 500x and analyzed for the presence of base substitutions, insertions/deletions, copy number alterations, and rearrangements. Results: 7 of 95 gliomas (7.4%) analyzed harbored BRAF alterations; 6 (6.3%) were identified with either a V600E mutation (3 GBM + 1 gliosarcoma) or a D594G mutation (2 GBM). One glioma with a BRAF rearrangement was identified (astrocytoma grade II). There were no alterations found in oligodendrogliomas. Molecular profiles in all 6 tumors with BRAF point mutations were similar; all were wild type for IDH1/2 and exhibited CDKN2A/B loss. Conversely, the BRAF rearrangement was IDH1 mutated and CDKN2A/B intact. To confirm the frequency of BRAF alterations, an independent database of 714 gliomas was queried. Thirty-four (4.8%) tumors were found to have BRAF alterations, including 24 BRAF point mutations. Of those, 96% (n = 23) were IDH1/2 wild type and 83% (n = 21) harbored CDKN2A/B loss. Conversely, BRAF rearrangements and amplifications (n = 10) did not share this profile. 40% harbored IDH1/2 mutations and only 40% displayed CDKN2A/B loss. In our patients, 5 of the 6 with BRAF point mutations are alive. The median overall survival is 28.8 months (10.7-40.6). One patient with recurrent GBM and V600E mutation was treated with the BRAF inhibitor vemurafenib with a PFS > 12 months. Conclusions: BRAF alterations occur in GBM and astrocytoma. BRAF point mutations are associated with a specific molecular profile, specifically IDH1/2 wild-type and CDKN2A/B loss. This profile identifies a molecular subgroup of gliomas that may exhibit improved survival and are amenable to targeted therapy with BRAF inhibitors.