Background and Objectives: Giant cell Tumor of bone (GCT) is often regarded as a benign tumor, but its clinical course is unpredictable, has a high rate of recurrence, and even can metastases and transform to a malignant tumor. Histological features of the tumor often could not predict its future biologic behavior, so it is just called ''Giant cell tumor'' without indicating malignancy or benignicity. Several methods are suggested to predict the biologic behavior of this tumor. This study evaluated the relation between Bax & bcl-2 as proteins involved in cell proliferation and death (apoptosis) with histopathologic features and clinical course of GCT. Materials & Methods: Paraffin- embedded tissue specimens of 40 GCTs of conventional, aggressive, recurrent, malignant, & metastatic types were evaluated by immunohistochemistry for Bax & bcl-2 markers. Clinicopathologic features and immunohistochemical results were statistically analyzed and presented in tables & diagrams. Results:Age, sex, and pattern of skeletal involvement were the same as other worldwide reports. Expression of Bax & bcl-2 markers were significantly higher in malignant GCTs but no statistically significant difference was found in other subtypes for bcl-2 while there was  statistically significant difference between subgroups for Bax. Conclusion:Considerable expression of Bax & bcl-2 markers in a GCT could signal its malignant course, but low expression is not valuable in predicting the clinical course. In addition, it seems that secondary tumor nodules in lung are just simple implantation not true malignant metastases