Background/Aims: Osteoblastoma and osteosarcoma are primary bone forming tumors that show different radiological/pathological features and clinical behavior. This study aims to specify the expression profile of Ki-67 and osteocalcin in osteoblastomas and osteosarcomas. Methods: Ki-67 and osteocalcin immunoexpression were studied in 9 osteoblastomas and 30 osteosarcomas; including 27 osteoblastic osteosarcomas. Results: There was gradual significant increase (p<0.01) in Ki-67 labeling index (Ki-67-LI) from osteoblastomas (23.7%), low grade osteosarcomas (58.8%), to high grade osteosarcomas (74.9%). Ki-67-LI in osteosarcomas was significantly higher than that in osteoblastomas (p<0.001). Osteocalcin was found in tumor cells of all osteosarcomas and osteoblastomas and in the osteoid matrix of 84% of osteosarcomas and 78% of osteoblastomas. Strong osteocalcin was significantly higher (p<0.02) in osteoblastomas (78%) than in osteosarcomas (27%). Conclusion: Ki-67 increased ongoing from osteoblastomas through low grade osteosarcomas, to high grade osteosarcomas and its estimation may help in the distinction between osteoblastomas and osteosarcomas. Intensity and distribution of osteocalcin may indicate the degree of osteoblastic differentiation