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. Ann Neurol 1999;45:403–406