EGFR amplification ( EGFR amp), the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10−), and TERT promoter mutation (p TERT mut) are alterations frequently observed in adult IDH -wild-type ( IDH wt) glioblastoma (GBM). In the absence of endothelial proliferation and/or necrosis, these alterations currently are considered to serve as a surrogate for upgrading IDH wt diffuse or anaplastic astrocytoma to GBM. Here, we set out to determine the distribution of EGFR amp, 7+/10−, and p TERT mut by analyzing high-resolution copy-number profiles and next-generation sequencing data of primary brain tumors. In addition, we addressed the question whether combinations of partial gains on chromosome 7 and partial losses on chromosome 10 exhibited a diagnostic and prognostic value similar to that of complete 7+/10−. Several such combinations proved relevant and were combined as the 7/10 signature. Our results demonstrate that EGFR amp and the 7/10 signature are closely associated with IDH wt GBM. In contrast, p TERT mut is less specific for IDH wt GBM. We conclude that, in the absence of endothelial proliferation and/or necrosis, the detection of EGFR amp is a very strong surrogate marker for the diagnosis of GBM in IDH wt diffuse astrocytic tumors. The 7/10 signature is also a strong surrogate marker. However, care should be taken to exclude pleomorphic xanthoastrocytoma. p TERT mut is less restricted to this entity and needs companion analysis by other molecular markers to serve as a surrogate for diagnosing IDH wt GBM. A combination of any two of EGFR amp, the 7/10 signature and p TERT mut, is highly specific for IDH wt GBM and the combination of all three alterations is frequent and exclusively seen in IDH wt GBM.