Abstract Background: The predictive role of radiological and histological classification of giant cell bone tumors has been disputed. Moreover, some malignant tumors including sarcoma and carcinoma harbor similarity with giant cell bone tumors. Application of molecular biomarkers can help to avoid these mimics and share for better understanding of its biological behavior. The current study investigates the immuno-histochemical expression of cyclinD1 and CD10 in giant cell bone tumors and analyzes their relation with clinico-pathological findings. Aim of Study: Evalute immune histochemical expression of Cyclin D1 & CD10 in giant cell tumors and analyze their relation with clinico-pathological finding. Material and Method: Immuno-histochemical expression of cyclin D1 and CD10 in 25 specimens of giant cell bone tumors were studied. The relationship between their expression and the clinico-pathological variables were also investigated. Results: Nuclear cyclin D 1 immuno-staining was observed in 40% of multi nuclear giant cells and complete absence in stromal cells in the same time the study found a statistical correlation between its expression and both of recurrence (p=0.001) and aggressiveness (p=0.012) of studied cases. Membranous CD10 immuno-expression was exclusively observed in 80% of stromal mononuclear cells with significant correlation with aggressiveness (p=0.23) and recurrence (p=0.014). Conclusion: Although radiological and histological clas-sification provides essential findings for giant cell bone tumor diagnosis, molecular markers (cyclin D1 and CD10) could be considered as independent predicting factors for GCT. Cyclin D1 can be considered as a prognostic marker to predict its behavior. CD10 is exclusively expressed in the neoplastic mononuclear cells, raising its possible role in the giant cell bone tumor pathogenesis.