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A 10-year-old spayed female mixed-breed dog was presented with a one-week history of inappetence and hyperthermia. Blood smear evaluation revealed the presence of rare atypical cells, raising suspicion for a circulating neoplasm. Spleen cytology, histopathology, and immunohistochemistry confirmed the diagnosis of hemophagocytic histiocytic sarcoma. The morphologic similarity between the atypical cells observed in the blood smear and those identified in the splenic cytology strongly suggests systemic dissemination of the disease.