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Toxoplasmosis is generally asymptomatic in immunocompetent individuals, but it can be life-threatening in immunocompromised patients. We present a case of a 62-year-old man with clinical features of acute appendicitis. Histology showed a transmural infiltrate of eosinophils. In addition, there were reactive lymphoid follicles with histiocytes in the submucosa and tachyzoites in the muscularis propria. Immunohistochemistry confirmed the diagnosis of toxoplasma appendicitis. Serological evaluation yielded negative results. Retrospective review of the history revealed that the patient was on long-term immunosuppressive therapy with methotrexate. The patient was treated with sulfamethoxazole-trimethoprim and is asymptomatic at 7-month follow-up. Toxoplasma appendicitis must be considered in the differential diagnosis of appendicitis in immunosuppressed patients.