Recent genomic advances have led to routine use of ATRX and IDH immunohistochemistry for glioma classification. Three adult patients (age range: 48-52 years) presented with focal neurological symptoms and intra-axial frontal mass lesions. Imaging features were atypical, and unusual features in two cases resulted in repeat imaging and diagnostic delay. On biopsy, all three were high-grade astrocytomas, but with variable histology, including pure GBM-PNET, and two anaplastic astrocytomas, one with gemistocytic features. All cases had diffuse ATRX loss by immunohistochemistry, strong diffuse nuclear TP53 positivity and MGMT promoter methylation. Immunohistochemistry and mutation analysis by SNaPshot single-nucleotide extension PCR for IDH1/2 mutations was negative. A SNaPshot assay revealed the G34R mutation in H3F3A in two cases. Mutations in H3F3A G34R were initially described in pediatric hemispheric high-grade gliomas, but this case series highlights that they may also be seen in older adults. While the prognostic significance of G34R mutations in adult glioma is unknown, testing should be strongly considered in any high-grade glioma with ATRX loss and wild-type IDH.