With the new 2021 classification system (WHO fifth edition), TERT promoter mutation, EGFR amplification, and +7/−10 copy number changes in IDH-wildtype diffuse astrocytomas are awarded a glioblastoma, IDH-wildtype CNS WHO grade 4 designation despite harboring histological features that would previously be rated as a lower grade. The gene discussed is IDH1; the disease is glioblastoma.