We describe a fatal case of amebic encephalitis caused by Balamuthia mandrillaris in a 3-year-old Czech boy who had never traveled abroad. This is the first such infection reported in Europe. The diagnosis was established by brain biopsy, in which abundant trophozoites and a few round amebic cysts were identified. The presence of multiple nucleoli in some trophozoites suggested the organism to be Balamuthia mandrillaris and this was confirmed by indirect immunofluorescence. The amebae invaded brain tissue, including neurons, and blood vessel walls, causing thrombovasculitis. The tissue reaction was a subacute necrotizing and granulomatous encephalitis (GAE) with an infiltrate of CD4- and CD8-positive T-lymphocytes, B-lymphocytes, plasma cells and macrophages. The child, in whom no underlying immunodeficiency was demonstrated, died after 45 days. The mode of infection was not established. Postmortem examination of the brain revealed massive areas of necrosis and microscopic findings like those in the surgical specimen. In vitro isolation of B. mandrillaris was unsuccessful.