H3-wildtype and IDH-wildtype gliomas are distinguished from diffuse midline gliomas (DMGs) by the retention of H3K27me3. To exclude infant-type hemispheric gliomas and desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA), molecular studies should be performed to check for NTRK, ROS1, ALK, and MET gene fusions. The gene discussed is IDH2; the disease is diffuse midline glioma.