Objective: To investigate the radiological and histopathological features of giant cell tumor of bone treated with RANKL inhibitor denosumab. Methods: Eleven cases were retrieved from the surgical pathology records between March 2015 and June 2017 in Beijing Jishuitan Hospital. Formalin fixed, paraffin embedded specimens were collected and the histological features were evaluated. The imaging features including X ray, magnetic resonance imaging, and computed tomography were also reviewed. Results: These 11 cases of giant cell tumor of bone were derived from five female and six male patients, with age ranged from 20 to 62 years (mean age, 35 years). The tumors were located in the sacrum (6 cases), femur (2 cases), radius (1 case), tibia (1 case) and patella (1 case), respectively. Histologically, all cases showed depletion of giant cells, proliferation of mononuclear cells and different degrees of ossification 3 to 6 months after denosumab therapy. Radiography showed marked osteosclerosis and sclerotic rim formation. Three cases of the sacrum recurred after 5, 6 and 11 months of surgery, and the remaining cases showed no recurrence within follow-up of 1 to 14 months. Conclusions Denosumab treated giant cell tumors morphologically differ from untreated tumors. Careful attention to a history of denosumab administration is crucial to avoid misdiagnosis and to allow proper differentiation from other tumors and tumor-like lesions.