Objective：To observe the expression of osteopontin (OPN) in the giant cell tumor of bone (GCTB) and to discuss its clinical significance.Methods: OPN expression was examined in 77 GCTB samples by EnVisionTM two-step immunohistochemical method. And the expression was compared between patients with different clinical and pathological data; the implied clinical relevance was also analyzed. Results: The positive expression rate of OPN in the GCTB was 76.6%; only weak expression was noted in the normal bone tissues. The expression in the invasive GCTB was significantly higher than that in the non-invasive ones（95.5% vs 69.1%, P=0.013）. The expression rate of OPN increased with the increase of Campanacci stages of GCTB, and significant difference was found between different stages（P=0.019）. The recurrence status, gender, age, surgery types, duration of illness or site of tumor were not associated with the positive rate of OPN. Conclusion: OPN is highly expressed in GCTB tissues, and the expression is associated with the invasiveness and the Campanacci stages of GCTB.