Immunohistological demonstration of osteonectin in normal bone tissue and in bone tumors. Osteonectin is a noncollagenous protein of bone which is believed to be bone specific, since its concentration in bone tissue is 500- to 1000-fold higher than in other connective tissues. Immunohistochemistry with polyclonal osteonectin antibodies shows a highly specific marking of actively matrix-producing osteoblasts. Osteonectin is involved in the process of osteoid maturation and mineralization. Immunohistochemistry of osteonectin antibodies proved to be a valuable tool in the diagnosis of bone tumors. Since osteonectin production seems to be an early event in the differentiation of cells of the osteoblastic lineage, immunoreactivity of osteonectin antibodies is observed in types of osteosarcoma lacking osteoid production (anaplastic, fibroblastic) while corresponding types of soft tissue tumors remain unstained.