A sphenoid mucocele often presents late due to its deep seated anatomical site. And it has varied presentation due to its loose relationship to the cavernous sinus and the base of the skull. We describe a case of large sphenoid sinus mucocele. A middle aged old man suddenly developed third cranial nerve palsy. Brain imaging study revealed an isolated sphenoid sinus mucocele, compressing right cavernous sinus. Endoscopic marsupialization of the mucocele via transnasal approach led to complete resolution of the third cranial nerve palsy. Involvement of the third cranial nerve in isolated mucocele is rare but important neurosurgical implications which must be excluded. In addition, proper and timely treatment must be performed to avoid permanent neurologic deficit.