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Percutaneous biopsy of petrous apex lesions is technically challenging due to deep skull base anatomy and proximity to critical neurovascular structures.1–5 In this technical video 1, we present a cone beam CT-guided biopsy using a contralateral subzygomatic transclival approach, initially described under CT guidance.6 The minimally invasive route provides a safe, direct trajectory to the petrous apex while preserving the internal carotid artery. The step-by-step workflow includes cone beam CT-based trajectory planning, fluoroscopic guidance, and coaxial bone sampling using an 11-gauge biopsy needle. Two clinical cases are demonstrated: one revealing metastatic breast cancer and another confirming Erdheim–Chester disease. Both procedures were completed without complications and allowed definitive histopathological diagnosis. This approach expands the interventional neuroradiologist’s toolkit for skull base access and represents a valuable alternative to open surgical biopsy in selected patients, combining precision, safety, and diagnostic efficacy. Video 1Cases presentation media110.1136/jnis-2025-024628.video016386909433112jnis-2025-024628media1