Cancer-related facial pain refractory to pharmacologic management or nondestructive means is a major indication for destructive pain surgery. Stereotactic mesencephalotomy can be a valuable procedure in the management of cancer pain involving the upper extremities or the face, with the assistance of magnetic resonance imaging (MRI) and electrophysiologic mapping. A 72-year-old man presented with a 3-year history of intractable left-sided facial pain. When pharmacologic and nondestructive measures failed to provide pain alleviation, he was reexamined and diagnosed with inoperable hard palate cancer with intracranial extension. During the concurrent chemoradiation treatment, his cancer-related facial pain was aggravated and became medically intractable. After careful consideration, MRI-based stereotactic mesencephalotomy was performed at a point 5 mm behind the posterior commissure, 6 mm lateral to and 5 mm below the intercommissural plane using a 2-mm electrode, with the temperature of the electrode raised to 80degrees C for 60 seconds. Up until now, the pain has been relatively well-controlled by intermittent intraventricular morphine injection and oral opioids, with the pain level remaining at visual analogue scale 4 or 5. Stereotactic mesencephalotomy with the use of high-resolution MRI and electrophysiologic localization is a valuable procedure in patients with cancer-related facial pain.