Insulin-like growth factor-binding protein-3 in osteosarcomas and normal bone tissues. To better understand the significance of local insulin-like growth factor-binding protein 3 (IGFBP-3) in the development of osteosarcoma, IGFBP-3 levels and subcellular localization were compared in biopsies from osteosarcomas and unaffected normal bone tissues.IGFBP-3 levels were analyzed by immunohistochemistry in 21 osteosarcomas and 5 unaffected bone tissues. IGFBP-3 levels were compared for patient outcome.Mature osteocytes of normal bone tissues contained high levels of predominantly nuclear IGFBP-3, whereas only 50% of osteosarcomas contained IGFBP-3-positive tumor cells, with predominantly cytoplasmic IGFBP-3 staining. Comparison of IGFBP-3 levels for patient outcome resulted in two groups. Patients with a low level of IGFBP-3 in osteosarcoma experienced a trend for a shorter survival time than did patients with a high level of IGFBP-3.Our results suggest that the levels and subcellular localization of local IGFBP-3 play a role in osteosarcoma development. Further prospective evaluation with higher clinical sample numbers might reveal a prognostic role for IGFBP-3 level in local tumors in patients with osteosarcoma.