Traditionally, Naegleria fowleri infections are labeled primary amebic meningoencephalitis because of prominent meningeal neutrophilic inflammation. Acanthamoeba spp. and Balamuthia mandrillaris are labeled granulomatous amebic encephalitis because of parenchymal granulomatous inflammation. We compared histopathologic and immunohistochemical features of 18 cases with central nervous system free-living ameba infections. Immunohistochemical assays using polyclonal antibodies that reacted specifically against each genus identified 11 patients with Balamuthia infection, four with N. fowleri, and three with Acanthamoeba. Immunohistochemical assays highlighted the presence of trophozoites that were difficult to identify with hematoxylin and eosin stains in areas of necrosis or where macrophages were abundant. Immunohistochemical assays also demonstrated the presence of granular antigens inside macrophages and blood vessel walls. Amebic cysts were observed in three patients with Acanthamoeba infection and in three with Balamuthia. Patients with Acanthamoeba infection showed granulomatous inflammation. Patients with Naegleria infection had neutrophilic inflammation. Balamuthia infections showed a spectrum of inflammation that ranged from primarily neutrophils to granulomas. Meningitis was present in 88% of cases. Immunohistochemical assays were useful to demonstrate the presence of granular antigens and confirmed the genus of the ameba. The spectrum of inflammation in cases of Balamuthia meningoencephalitis is broader than previously described. The term amebic meningoencephalitis describes better the histopathologic findings than the currently used classification of primary amebic meningoencephalitis and granulomatous amebic encephalitis.