The differential diagnosis of large cystic brain lesions is wide. In the UK the most likely is tumour but infection should be considered. We present the case of a 47-year-old Indian man with such lesions and an unexpected pathological diagnosis. Mr S attended MAU in March 2008 with confusion, agitation and a subacute left hemiparesis. MRI brain showed three large peripherally enhancing cystic lesions in both frontal lobes and right temporal lobe with significant mass effect. There were no other lesions. Histology unexpectedly demonstrated reactive gliosis, perivascular lymphocytic infiltrate and white matter myelin loss with no evidence of infection or tumour. Post-operatively he had a dense hemiplegia and frontal lobe syndrome with aggression, coprolalia (Punjabi but subsequently also English), hyperphagia and disinhibition which lasted several months, making treatment, nursing, rehabilitation and placement extremely difficult. He spent 280 days on the acute neurology ward before transfer to a nursing home. Interrogation of previous medical records and questioning of family members revealed a previous history of unexplained visual loss with bilateral steroid-responsive papillitis in 2004 that had not recurred. Brain CT and CSF examination, including oligoclonal bands, were normal. Megacystic multiple sclerosis is a rare variant. Few cases have been reported in the literature. We remind neurologists that it is a differential diagnosis of brain cysts and review the literature.