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These downloadable slides on the neurosurgical management of H3 K27-altered diffuse midline glioma (DMG) focus on the role of stereotactic biopsy, molecular diagnosis, and treatment planning. Topics include evaluating the risks and benefits of tissue acquisition based on tumor location and clinical presentation; optimizing biopsy techniques and tissue stewardship to support integrated molecular diagnosis; and interpreting H3 K27M immunohistochemistry, H3K27me3 assessment, sequencing, and cerebrospinal fluid tumor DNA testing. The slides also review clinical evidence supporting dordaviprone in progressive H3 K27–mutant DMG, the ongoing phase III ACTION trial, and investigational approaches including ONC206 and CAR T-cell therapies targeting GD2 and B7-H3. Additional considerations include managing neurologic deterioration and hydrocephalus, coordinating multidisciplinary care, and optimizing referral timing and procedural planning to preserve treatment and clinical trial opportunities.