BACKGROUND Hereditary progressive mucinous histiocytosis was first described in 1988. The clinical features of this probably autosomal dominant inherited disease are skin-colored or red pea-sized tumors all over the skin appearing in the first decades of life and increasing gradually in number throughout life. In contrast to other benign histiocytic skin diseases there is no spontaneous tumor resolution. RESULTS A 52-year-old woman and her 25-year-old daughter of a further family are reported. Both showed similar longstanding lesions without tumor regression. There was no evidence of visceral involvement. Histologic, immunohistochemical, and ultrastructural examinations revealed histiocytes from the monocyte/macrophage subset as the main constituents of the tumors. The cells contained abundant zebra and myeloid bodies and vacuoles indicating a lysosomal storage disease. Special investigations, however, such as lymphocytic storage, thin-layer chromatography of the involved tissue, lysosomal enzymes in serum, and enzymes released from cultured fibroblasts showed negative results. A pathologic accumulation of mucopolysaccharides or phospholipids in serum or urine or a basic enzyme defect could not be detected. CONCLUSIONS Hereditary progressive mucinous histiocytosis has been previously reported in seven patients, all of whom were female. A pathologic proliferation of histiocytic cells from the monocyte/macrophage subset with lysosomal storage phenomena gives rise to the clinical symptoms. The disease does not correspond to one of the known lysosomal storage diseases. Since exact information on the stored material is still lacking, it cannot be ruled out that the disease is not primarily a true storage disease but a proliferation and accumulation of macrophages due to a hitherto unknown and persistent stimulus.