Sixteen cases of typical highly malignant osteosarcoma were investigated by light, electron, and immunofluorescence microscopy to demonstrate the presence of collagen types I-III. It was shown that, in light-microscopically anaplastic areas of the tumor, collagen type III predominates, while only very few membranes of collagen type I are observed. Ultrastructurally, the cells are characterized by numerous free ribosomes in their cytoplasm and only a few membranes of granular endoplasmic reticulum (ER). In osteoblastic areas, collagen type I is increased, while type-III collagen is decreased. The cytoplasm of cells contains markedly more granular ER. An increasing mineralization of matrix is observed. In fibroblastic areas of the tumors, collagen types I and III are codistributed. Tumor cells have a fibroblast appearance with elongated nuclei and well developed granular ER. The chondroblastic areas, characterized by immature neoplastic cartilage, contain varying amounts of collagen type II. Chondroblast-like tumor cells have typical ring-shaped membranes of granular ER in their cytoplasm. The evidence of different collagen types in osteosarcomas lends additional support to the concept that a pluripotent mesenchymal cell is the stem cell of osteosarcomas.