Biochemical markers of bone metabolism have been used in medicine to evaluate and provide treatment to patients with metabolic bone diseases, such as osteoporosis. Serum cross-linked C-telopeptide of type I collagen (CTX) is a marker of osteoclast activity and is used to assess the level of bone resorption. Recently, in oral and maxillofacial surgery, it was proposed that the levels of serum CTX may predict the subsequent risk of developing osteonecrosis of the jaws (ONJ) after oral surgery procedures for patients taking oral bisphosphonates (BPs). The goal of this study was to determine whether this specific serum marker of bone resorption could preoperatively predict the risk of developing ONJ from oral BPs.We hypothesized that there is no clinical correlation between the observed preoperative serum CTX values and the risk of developing ONJ. The authors examine the scientific basis (validity) of the morning fasting serum CTX test in 163 consecutive patients who underwent various oral surgery procedures in the office. The authors also review the laboratory test results and the recommended protocol based on the test values. One hundred sixty-three patients (mean age, 75.9 years) were divided into 2 groups. Group I was the control group that consisted of 109 patients taking oral BPs who did not take the CTX test preoperatively. Group 2 consisted of 54 patients taking BPs and who elected to have the CTX test performed to assess their level of risk of developing ONJ, preoperatively. Both groups of patients were observed for a period of 8 weeks for signs and symptoms of BP-associated ONJ after surgery. The clinical data at 8 weeks and beyond revealed that there was no evidence of BP-associated ONJ in all participants. We conclude that the serum CTX is not a valid preoperative test to accurately assess the level of risk of developing ONJ and is not indicated in the oral surgery patient.