According to the most recent 2021 WHO classification of CNS tumors, along with IDH characterization and a “typical” histopathological background constituting glioblastoma habitat, further molecular characterization over telomerase reverse transcriptase promoter (TERT) expression, epidermal growth factor receptor (EGFR) amplification and aneuploidy is required to label a grade 4 glioma as glioblastoma. This evidence concerns the gene EGFR and glioblastoma.