Cerebral tumor-like American trypanosomiasis (CTLAT) is an uncommon complication of Chagas' disease, observed only in immunosuppressed patients. We assessed 10 human immunodeficiency virus-positive patients with Chagas' disease who presented with CTLAT. All patients had neurological involvement and 6 developed intracranial hypertension. Neuroimaging studies showed supratentorial lesions in 9 patients, being single in 8. One case had infratentorial and supratentorial lesions. Low CD4+ cell counts were observed in all the cases and in 6 of them CTLAT was the first manifestation of acquired immunodeficiency syndrome. Serological tests for Chagas' disease were positive in 6 of 8 patients. Trypanosoma cruzi was identified in all brain specimens and in three cerebrospinal fluid samples. CTLAT should be considered in the differential diagnosis of intracranial mass lesions in human immunodeficiency virus-positive patients and should be added to the list of acquired immunodeficiency syndrome-defining illnesses.