A 50-year-old Chinese man presented with rapidly progressive unilateral ophthalmoplegia and then an ipsilateral afferent pupil defect. CT and MRI revealed a mass centered in the anterior clinoid process causing bone destruction and showing high T1 and T2 signal intensity indicative of mucosal protein secretion. These imaging features suggested a mucocele, which may have resulted from sequestration of a clinoidal extension of the sphenoid sinus. The sphenoid sinus was opened via an image-guided endoscopic approach, and the lesion incised. There were no complications. The ophthalmoplegia and afferent pupil defect had completely resolved within 1 week of surgery. This is the eighth reported case of anterior clinoidal mucocele, a rare cause of ophthalmoplegia or optic neuropathy. Advances in endoscopic instrumentation, navigation systems, and intraoperative imaging have reduced the operative risk and made the endoscopic approach a feasible and safer alternative to open surgery for this condition.