Abstract: Osteosarcoma along with other tumors like osteoma, osteoid osteoma and osteoblastoma are grouped as bone forming tumors. Several studies have shown link between serum concentrations of IGF-I and increased risk of common cancers namely breast, prostate, colorectal and lung cancer. Conflicting data are available regarding leptin effects on bone with both positive and negative effects being reported. No reports are available regarding leptin levels in osteosarcoma and its correlation with IGF-I. Hence, the present study is planned to study serum IGF-I and leptin levels in patients of osteosarcoma. Serum IGF-1 and leptin were analyzed in thirty cases of osteosarcoma and these patients were compared with thirty age and sex matched controls with musculoskeletal pain. Serum calcium and phosphorous levels were decreased in patients with osteosarcoma as compared to controls. Serum alkaline phosphatase levels were significantly raised in patients with osteosarcoma as compared to patients of musculoskeletal pain (p<0.001). Serum IGF-1and leptin levels were significantly decreased in osteosarcoma patients (group-II) as compared to the patients of musculoskeletal pain (group-I), (p<0.001, p<0.05, respectively). Inverse correlation was observed between IGF-1 and calcium, IGF-1 and ALP, leptin and calcium leptin and ALP in group II as compared to group I. Lowered serum IGF-1 and leptin levels observed in osteosarcoma patients as compared to control in the present study and could be due to their possible utilization in tumor formation. The present study suggests that these parameters can serve as useful markers for diagnosis and follow up of disease.