Context: Osteosarcoma is a rare malignant bone tumor, commonly occurring in the age group of 10 to 24 years. Recent reports have indicated that there is a link between fluoride exposure and osteosarcoma. Aims: The present study was planned to analyze serum levels of fluoride in patients of osteosarcoma and fluoride content of their drinking water. Settings and Design: The present study was carried out comparing 10 patients of osteosarcoma and 10 healthy volunteers (who served as controls). Materials and Methods: Serum and drinking water fluoride levels were estimated by ion selective electrode. Statistical analysis used: The data were computed as mean ± SD and Student′s t test was applied. Results: Both, the serum and drinking water fluoride levels, were significant by higher in patients with osteosarcoma as compared to controls (P < 0.05, P < 0.001, respectively). Conclusions: These results suggest a link between fluoride exposure and osteosarcoma.