BACKGROUND : Clearpoint Smartframe is a magnetic resonance imaging-compatible stereotactic system often used to perform magnetic resonance imaging-guided biopsies. The system is typically mounted on the scalp through screws that pierce the skin and penetrate the outer table of the cranium. However, the frame can also be configured to be mounted directly onto the skull. METHODS : Here, we describe the clinical context well suited for a skull-mount Clearpoint Smartframe surgery. The patient suffered from a subcentimeter right parafourth ventricular contrast-enhancing lesion with hydrocephalus and underwent a right suboccipital needle biopsy followed by an occipital ventriculoperitoneal shunt. Although the hydrocephalus resolved with the ventriculoperitoneal shunt, the biopsy sample proved nondiagnostic. The patient underwent a second procedure during which the Clearpoint Smartframe was mounted onto the skull through space dissected free during the previous surgery. Diagnostic biopsy (H3K27 glioma) was performed followed by stereotactic laser ablation of the lesion. CONCLUSIONS : We describe a case in which the skull mount Clearpoint Smartframe was used to biopsy and ablate a midline H3K27 glioma.