Myeloid sarcoma (MS) is a neoplasm of immature granulocytes, monocytes, or both involving extramedullary sites. MS with no evidence of leukemia (nonleukemic MS) is very rare and the initial diagnosis can be difficult. This report describes an unusual case of nonleukemic MS of the liver in a 16-year-old patient presenting as debilitating hepatomegaly. A liver biopsy revealed diffuse infiltration by neoplastic cells of myeloid lineage (CD68, myeloperoxidase). A bone marrow biopsy showed no evidence of medullary involvement. The patient subsequently developed heart failure. Autopsy revealed infiltration of most organs by neoplastic cells but failed to identify abnormal myeloid cells in bone marrow.