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The clinical and radiological findings of a patient affected by apoplexy of an adenoma located within cavernous sinus and presenting isolated Cranial Nerve (CN) VI palsy are reported. The differential diagnosis with other pathologies is debated, and pathogenesis of isolated abducens nerve palsy is investigated. The pertinent literature of this uncommon case of apoplexy is reviewed. A 59-year-old female presented sudden appearance of CN VI palsy associated to violent headache. Endocrinological assessment did not show pituitary insufficiency; MRI depicted an adenoma located within the left CS. She underwent an endoscopic endonasal procedure with extensive opening of the cavernous sinus, occupied by an ischemic adenoma. Afterward, neurological symptoms promptly resolved and the patient was discharged after 5 days. At 3 months follow-up MRI radical tumor removal was assessed, and the patient resulted neurologically intact. The review of the pertinent literature shows that apoplexy of pituitary tumor exclusively located within the Cavernous Sinus is a very uncommon event. The distinctive clinical presentation is represented by the sudden abducens nerve palsy and the absence of pituitary insufficiency and it could be explained by the vulnerability of the nerve along its course within the cavernous sinus, and by the sparing of the sellar content by the adenoma. © 2011 Springer Science+Business Media, LLC.