In an effort to better understand the biology of “IDH-mutant astrocytoma with EGFR amplification,” we present the clinical and molecular profiles in four such rare cases encountered at two institutions; evaluate them based on cytogenetics, DNA sequencing, and DNA methylation profiling; and scrutinize published datasets for this specific entity to gain further insight into its diagnostic and prognostic implications. The gene discussed is IDH1; the disease is astrocytoma (excluding glioblastoma).