Mutations in IDH1 and IDH2 (most commonly the IDH1 R132H variant) define the majority of histologically lower-grade diffuse gliomas as well as what was previously termed “secondary glioblastoma” (i.e., tumors with grade 4 histology and documented radiologic and/or histopathologic evolution from lower-grade gliomas). The gene discussed is IDH2; the disease is glioma.