Two unrelated adult sibling cases (36- and 32-year-old females) of juvenile hyaline fibromatosis are presented. The parents of one of these patients were non-consanguineous but natives of a small island, and one elder sister among four siblings was affected with the same disease. The parents of the other patient were consanguineous, and one other sibling suffered from the identical disease. Both patients presented with multiple subcutaneous nodules, which they had had since infancy, and had undergone numerous surgical excisions. Light microscopy examination of skin lesions from both patients showed identical histology; an abundance of a homogenous, amorphous, eosinophilic extracellular matrix in which spindle-shaped cells were embedded. Electron microscopically, the spindle-shaped cells had hypertrophic Golgi apparatus and dilated, rough endoplasmic reticulum. Fine fibrillar and granular material-filled structures, the contents of which were occasionally released into the extracellular matrix, were also seen. Immunohistochemically, the spindle-shaped cells were vimentin-positive but negative for α-smooth muscle actin and S-100 protein, and the hyaline ground substance was positive for type I and type III collagen but negative for type II and type IV collagen and tenascin. Matrix metalloproteinase-1, -2, and -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2 was positive but TIMP-1 was negative. A review of 39 cases of juvenile hyaline fibromatosis in the literature is also presented. In summary, skin lesions may be the most outstanding symptoms of juvenile hyaline fibromatosis, but joint contracture and gingival hypertrophy precede the skin manifestation.