We report a case of a very rare disorder, histiocytic sarcoma, from a review of our autopsy cases. The neoplastic cells that proliferated in organs throughout the body were large cells containing eosinophilic cytoplasm and pleomorphic nuclei with prominent nucleoli. In the bone marrow, erythrophagocytosis by neoplastic cells was observed. The neoplastic cells were positive not only for lysozymes and CD68 (KP-1, PG-M1, and Ki-M1P) but also for a monocyte/macrophage-specific marker, CD163. In contrast, the results of tests for markers of myeloid cells, lymphoid cells, and epithelial cells were all negative. In a polymerase chain reaction study of paraffin-embedded tissues, analyses for the rearrangement of immunoglobulin heavy chain and T-cell receptor-gamma genes were negative. The current World Health Organization diagnostic criteria for histiocytic sarcoma regard immunohistochemical investigation as crucial. In this regard, the highly specific positivity for CD163 in this patient indicates that immunohistochemical staining of CD163 is very useful for the diagnosis of histiocytic sarcoma.