Background: IDH mutational status is required for diagnosis according to the 2016 WHO criteria. The single nucleotide polymorphism (SNP) rs11554137 (IDH1^105GGT) at codon 105 of IDH1 has been reported in patients with several tumor types, including glioma. The aim of this study is to investigate the prognostic role of IDH1^105GGTMethods: We analyzed our institutional data warehouse for consecutive patients (pts) with newly diagnosed, histologically proven grade II or Grade III gliomas. IDH sequencing was performed using the 454 GS-Junior next generation sequencer (NGS) (Roche Diagnostic, Mannheim, Germany). All analyses were performed on DNA from formalin fixed and paraffin embedded (FFPE) specimens. Results: The analysis included 77 pts with grade II (n = 51, 66.2%) or grade III glioma (n = 26, 33.8%). Median follow up of this study was 91 months. Patients received biopsy/partial resection/complete resection in 7.8%, 70.1% and 22.1%, respectively. Postsurgical RT and/or chemotherapy was delivered in 64.9% of pts. IDH mutations affecting codons 132 (for IDH1) and 172 (for IDH2) were found in 71 pts (92.2%). IDH1^105GGTwas found in 11 pts (14.3%), mainly harboring also IDH mutations (81.8%), and was more frequent in grade 3 (30.8%) than in grade 2 gliomas (5.9%, P = 0.006). Pts harboring both IDH mutations and IDH1^105GGTshowed a significantly longer progression-free survival compared with pts with IDH mutation alone (78.7 months vs 49.9 months, p = 0.041). Conclusions:IDH1^105GGT represents a promising novel biomarker in IDH mutated grade 2 and 3 gliomas and warrants further investigations.