Identification of a subpopulation of G-CIMP-high tumors carrying the worst prognosis has crucial clinical implications for the assessment and therapeutic management of individual aggressive LGGs at risk for malignant recurrences and acquisition of an IDH-wild-type and stem cell-like glioblastoma phenotype that could not be predicted by histopathological grading at primary diagnosis. The gene discussed is IDH1; the disease is glioblastoma.