This report is a case of histiocytic sarcoma (HS), in which tumor cells consist of two immunohistopathologically distinct populations (A) oval CD68+lysozyme+CD163- cells and (B) abundant cytoplasm or spindle-shaped CD68+lysozyme-CD163+ cells. Cervical lymph node was infiltrated mainly by population (A), where chemotherapy was quite effective. On the other hand, vast majority of infiltrated tumor cells in the hilar lymph node belonged to population (B), in which the cells were resistant to chemo-radiotherapy. Considering the poor prognosis of HS, the expression of CD163 could be a marker for resistance to chemo-radiotherapy. It is also notable that CD163-negative stage of HS may exist and still be reactive for the treatment.