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Introduction: Cavitary white matter changes are mainly described in leukodystrophies and especially in vanishing white matter disease. Large cavitary lesions are not typical for multiple sclerosis (MS)., 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), vanishing white matter disease genetic analysis, and MRI characteristics of the cavitary lesions were analyzed., Results: Twenty patients were analyzed (6 men and 14 women). Mean age at disease onset was 37.6 (range 17-58). Mean disease duration was 10 years (range 2-20). Five patients had initial relapsing-remitting MS and nine patients had primary-progressive MS. Mean EDSS was 5.5 (range 2-8). Mean MMS was 20/30. Vanishing white matter disease genetic analysis was performed and negative in seven 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 a MS subgroup, predominantly women, with relatively late disease onset, predominantly primary-progressive type, relatively high EDSS scores, and severe cognitive dysfunction., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)