Malakoplakia is an unusual chronic inflammatory disease occurring predominantly in the bladder and only rarely affecting other organs. For the urinary tract, its aetiology has been ascribed to the presence of Escherichia coli, while the very few cases of cerebral malakoplakia which have been reported so far, have mostly occurred in infants in the clinical setting of neonatal herpes virus infection or otherwise in adults in areas of cerebral infarction. We here report a case of E. coli-associated malakoplakia of the brain. It occurred in a 53-year-old man who had undergone long-term corticosteroid therapy and had previously been operated on a cerebral E. coli-associated abscess. This case indicates that malakoplakia of the brain might also be a histiocytic reaction against bacterial antigens of the E. coli family.