The light- and electron-microscopic features and histochemical characterization of 3 consecutive cases of malignant histiocytosis (MH) are reported. Each case demonstrated involvement of lymph nodes and bone marrow. In the lymph node, the characteristic destructive sinusoidal pattern of involvement by cytologically malignant cells was present. Phagocytosis by malignant cells was rare and most readily appreciated in the imprint preparations. The major problem in differential diagnosis is related to defining the histiocytic nature of the malignant cells. This question was resolved by the demonstration of diffuse cytoplasmic staining with the nonspecific esterase and acid phosphatase reactions as well as the ultrastructural demonstration of histiocytes. Although benign, reactive histiocytes were positive, malignant histiocytes did not stain for lysozyme by an immunoperoxidase technique. In contrast to the uniform appearance of these cases, many reports of MH in the past have consisted of heterogeneous cases with variable histologic appearances from a proliferation of predominantly mature histiocytes with marked phagocytosis to cytologically malignant cells with little apparent functional activity. This variation in histologic appearance is due in part to inclusion of cases of reactive histiocytic proliferations, including the recently described virus-associated hemophagocytic syndrome.