A unique case of malignant histiocytosis (MH) is reported. Its origin from the monocyte-macrophage system was indicated by expression of highly specific myeloid cell markers (My4, MCS2, and cytoplasmic lysozyme), diffuse activity of acid phosphatase and NaF-sensitive alpha-naphthyl acetate esterase, lack of immunologic markers specific for other cell lineages, and germ line configuration of the immunoglobulin light chain gene and the T-cell receptor beta-chain gene. Its neoplastic nature was suggested by the single rearranged band of the immunoglobulin heavy chain gene.