Midline malignant reticulosis (MMR), a disease included in the lethal midline granuloma, is histologically characterized by a mixture of lymphoid cells and atypical reticulum cells. Recent investigations of the nature of proliferating cells in MMR have suggested different conclusions, i.e., that the lesion is a true histiocytic, B- or T-cell. Two cases of MMR are presented, on which extensive laboratory studies were carried out. The results showed that the atypical reticulum cells were negative when stained immunohistochemically with monoclonal antibodies for T- or B-cells, diffusely stained by reactions for acid phosphatase and alpha-naphthyl acetate esterase, positively stained with human lysozyme and alpha-1-antitrypsin, and possess abundant cytoplasm containing primary lysosomes, polylysosomes and residual bodies. These findings indicate the true histiocytic nature of the proliferating cells in MMR.