<p>The median medullary perforators, a group of perforator vessels arising from the vertebrobasilar junction, remain underrecognized. There is scarce knowledge regarding their clinical significance&#xa0;and relevance in foramen magnum surgery. This study elucidates the anatomy of these perforators and their clinical and surgical relevance, in analogy to the well-known vital basilar tip perforators. We highlight their potential contribution to selective pyramidal infarct or ischemia during foramen magnum tumor resection, and rarely their implication in isolated ischemic strokes of the medullary pyramid.&#xa0;The anatomical study included six formalin-fixed cadaver specimens with latex, India ink, ICG, and gadolinium-injected brainstem vessels. The intrinsic distribution of the median medullary perforators was visualized grossly, histologically, and by micro-MRI. We also reviewed ten operative videos of ventral foramen magnum meningioma cases to assess intraoperative identification and preservation of these vessels. One unique clinical case with pure bilateral pyramidal ischemia manifesting as dense quadriplegia was readdressed.&#xa0;Gross inspection showed various origins of these perforators, mainly from the lower basilar segment and the junction of the vertebral arteries, which coursed towards the caecum and anterior median fissure. Injection of the isolated vertebrobasilar junction with India ink, ICG, and contrast revealed short vessels that supplied the pyramids exclusively, and longer perforators coursing medially.&#xa0;Distinct short perforators were identified predominantly supplying the pyramids, arising from the vertebral artery distal to, and separate from, the anterior spinal artery. Intraoperative video confirmed the presence of the median medullary perforators and their potential in causing grave isolated pyramidal ischemia.</p>