Background: We have shown the significance of NF1 mutations(mut) in a group of high grade gliomas, and their association with IDH mut. The significance of TERT has also been shown. However, the role of TERT in the setting of NF1 mut is not known. Methods: A total of 101 patients with grade III-IV gliomas treated with standard of care were included in the analysis. While 55 genes were tested by NGS, mut were found in 37 and where included in the analysis. TERT was tested with Sanger sequencing. Results: The median age was 54.7 years, most patients were males (57.4%) and most had undergone a subtotal tumor resection (59.4%). 85 patients were diagnosed with grade IV gliomas, while 16 had grade III tumors. TERT, TP53, IDH, EGFR, PTEN and NF1 were the most frequently mutated genes. 72 tumors carried TERT mut, 24 had wild-type(WT) TERT, while for 5 patients the status of TERT was unknown. TP53 and IDH mut were found in 24.8% and 13.9% of the tumors, respectively, while 14.9% carried EGFR mut. 23 patients had WT TERT and NF1, 66 had WT NF1 and mutated TERT, 6 patients had mut in both genes and in one tumor TERT was WT and NF1 was mutated. Mutated TERT was more frequently observed in patients with WT IDH and TP53 (p = 0.019 and p = 0.006, respectively), while WT TP53 was associated with WT IDH (p < 0.001). With a median follow-up of 82.3 months (mos), 87 patients have died. The median overall survival (OS) is 22 mos (95% CI 17.3-27.9), while the 12-mo OS rate is 74.3%. Among patients with WT TERT and NF1, the median OS was 40.82 (95% CI 28.10-94.10), while among patients with WT NF1 and mutated TERT it was 18.46 (95% CI 14.89-22.00). Patients with mutated NF1 and TERT experienced worse OS than those without (HR = 3.19, 95% CI 1.44-7.06, p = 0.004 and HR = 2.26, 95% CI 1.33-3.84, p = 0.003, respectively), while patients with mut in IDH were at lower risk of death (HR = 0.24, 95% CI 0.11-0.52, p < 0.001). Upon multivariate analysis, TERT did not retain its unfavorable prognostic significance for OS either when adjusting for age and NF1 mutational status (p = 0.13) or in the model adjusting for age and IDH mutational status (p = 0.21). Conclusions: TERT seems to lose its importance in the face of NF1. IDH with NF1 may suffice to identify three groups with distinct prognosis.