Background/aim: Osteosarcoma requires an angiogenesis process. CYR61 is one of the extracellular signaling molecules that promote angiogenesis, tumor growth, and the malignancy of osteosarcoma. In the present study, we investigate the CYR61 gene variations in osteosarcoma and their correlations with clinicopathological findings. Materials and methods: We performed variation analysis of the CYR61 gene in 58 patients with osteosarcoma. With an aim to ascertain the variety of variations in exons 2, 3, 4, and 5 of the CYR61 gene in osteosarcoma, we did a PCR-SSCP followed by DNA sequencing. Results: In osteosarcoma the CYR61 gene variations found were 18.96% (11/58) in exon 2, 3.44% (2/58) in exon 3, 8.62% (5/58) in exon 4, and 15.51% (9/58) in exon 5. In our variation analysis, we detected one missense variation in exon 2 (Arg47Trp), one silent variation in exon 3 (Lys152Lys), one missense variation in exon 4 (Phe213Leu), and two missense variations in exon 5 (Gly315Arg and Asp339Asn). The overall CYR61 variation frequency in exons 2, 3, 4, and 5 was determined to be 46.55% (27/58). Conclusion: Our study specifies the role of CYR61 gene variation in osteosarcoma. The result signifies that CYR61