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Craniopharyngiomas (CPs) are benign tumors that are believed to arise from embryonic remnants of the Rathke pouch epithelium. Herein, we report a case of aseptic meningitis due to spontaneous rupture of multicystic CP, which contained an Ommaya catheter. A 19-year-old boy was admitted to the hospital with a 4-day history of acute severe headache after strenuous physical exercise followed by altered sensorium, fever, and neck stiffness. Cerebrospinal fluid (CSF) analysis revealed marked pleocytosis and elevated protein levels. CSF culture was otherwise negative. Cyst reduction on subsequent imaging confirmed the diagnosis. The patient received intravenous steroid therapy and was discharged asymptomatic. This is a rare evolution of a multicystic CP, which was previously treated with intracystic therapy and had an Ommaya catheter. Clinicians should be aware of spontaneous CP rupture and look actively for the occurrence of cholesterol crystals or elevated CSF levels of cholesterol as well as prompt follow-up imaging.