BACKGROUND AND PURPOSE: Subdural empyema represents a loculated infection between the dura and the arachnoid. It has been described either intracranially or in the spinal canal, the latter localization being quite rare. While treatment guidelines for a single (either brain or spinal) localization of a subdural empyema are more or less established, its management when a massive involvement of CNS is evident represents a challenge. METHODS: The authors describe a unique case of a 65-year-old woman having a massive involvement of the entire CNS with multiple localizations, both intracranial and spinal. Early diagnosis was obtained through brain CT scans followed by cranio-spinal contrast enhanced MRI scans. Patient was treated with external ventricular drainage and suboccipital craniectomy, while on antibiotic therapy. RESULTS: Patient's neurological condition gradually improved. By the end of the eighth hospital week, she was discharged without any neurological deficit. CONCLUSIONS: Spinal subdural empyema and brain subdural empyema are not always, as in our case, two different entities. Prompt diagnosis and treatment constitute the major variables affecting outcome. © 2007 by the American Society of Neuroimaging.