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Background: Large cavitary lesions are not typical for multiple sclerosis (MS). Cavitary white matter changes may be seen in megalencephalic leukoencephalopathy with subcortical cysts, Alexander disease, mitochondrial leukoencephalopathies, vanishing white matter disease, leukoencephalopathy with calcifications and cysts, cytomegalovirus infection, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy., Objective: To analyze clinical and radiological characteristics in MS patients with large cavitary lesions., Methods: We studied MS patients with large cavitary brain lesions. Patient characteristics, disease onset/duration/subtype, expanded disability status scale (EDSS), mini mental state (MMS), corpus callosum lesions, history of segmental myelitis, CSF oligoclonal bands (OCB), visual evoked potentials (VEP), vanishing white matter disease genetic analysis, and characteristics of the cavitary lesions were analyzed., Results: Nine patients were analyzed, 1 man and 8 women. Mean age of disease onset was 38.5 years. Mean disease duration was 9 years. Three patients had initial relapsing-remitting MS and 6 patients had primary-progressive MS. Mean EDSS was 4.5. Mean MMS was 20/30. Segmental myelitis was present in 6 cases. OCB were found in 6 patients. VEP was performed in 6 patients, and pathological in all but one. Vanishing white matter disease genetic analysis was performed and negative in 5 patients. Inferior corpus callosum lesions were seen in all patients with available sagittal FLAIR sequences. Cavitary lesions were strictly supratentorial, and located inside the diffuse leukoencephalopathy, with often a posterior predominance., Conclusion: MS patients with large cavitary lesions seem to represent an MS subgroup, predominantly women, with relatively late disease onset, predominantly primary-progressive type, relatively high EDSS scores, and severe cognitive dysfunction., (Copyright © 2012 S. Karger AG, Basel.)