In this report, we describe four cases of granulomatous amebic encephalitis caused by Balamuthia (Leptomyxid ameba) in four previously healthy Mexican patients. All four cases were characterized by focal neurologic signs, increased intracranial pressure, and cerebral hyperdense lesions in computed tomography scans of the head. These patients underwent craniotomies for evaluation of mass lesions for possible brain tumors. Granulomatous chronic inflammatory reaction and amebic trophozoites were found in brain biopsies. At autopsy, areas of hemorrhagic encephalomalacia were located in both basal frontal lobes, right parieto-occipital lobes, and, less often, in the brainstem and cerebellum. Angiitis, necrotizing granulomatous encephalitis, and large numbers of amebic trophozoites in perivascular spaces were present. Amebic trophozoites were seen in the left adrenal gland in one of the cases. The amebas in all four cases were identified as Balamuthia mandrillaris (Leptomyxiidae) based on their reactivity with the anti-Balamuthia (Leptomyxiidae) serum in an immunofluorescence test.