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Entamoeba dispar, belonging to the Genus Entamoeba along with Entamoeba histolytica that causes amebiasis, was previously considered a non-pathogenic ameba and an ideal model for studying the pathogenesis of amebiasis. However, since its strains were isolated from symptomatic patients in Brazil in 1996, its pathogenic potential has been a subject of discussion. We report a case of multiple granulomatous encephalitis in a 4-year-old immunocompetent boy presenting with left eye esotropia. Sequences of E. dispar were detected in his cerebrospinal fluid through Next-Generation Sequencing (NGS). After three courses of metronidazole therapy, the brain and lung lesions showed significant reduction in subsequent examinations. This case expands the spectrum of diseases associated with E. dispar.