Background and Aims: A group of osteogenic bone tumors can be diagnostically challenging at the histopathological level. These include aggressive osteoblastoma and osteoblastoma-like osteosarcoma. This study aimed at assessing the utility of Ki-67 labeling index in the differentiation between these types of neoplasms. Methods: A total of 39 patients were enrolled in this study, including 9 osteoblastomas (6 conventional and 3 aggressive types) and 30 osteosarcomas (20 high grade and 10 low grade). Immunohistochemical staining using Ki-67 antibody was done. Ki-67 labeling index was calculated and statistically compared between the different groups of tumors. Results: There was gradual significant increase (p<0.05) in Ki-67 labeling index from osteoblastomas, through low grade osteosarcomas, to high grade osteosarcomas. There was also significant difference (p<0.001) in proliferation index between aggressive osteoblastoma and low-grade osteosarcoma. Conclusion: Our results suggest that estimation of the proliferation index may help in the distinction between aggressive osteoblastomas and osteoblastoma-like osteosarcoma. However, careful interpretation of the clinical, radiological and histopathological features remains essential to reach proper diagnosis.