Objective: To study the clinical significance of serum pyridinoline cross-linked C-telopeptides of type I collagen (I CTP) and bone sialoprotein (BSP) to diagnose bone metastases in patients with thyroid cancer. Methods: A total of 102 patients with thyroid cancer were enrolled and allocated into 2 groups: Bone metastasis group and non-bone metastasis group. The bone metastasis group was assigned into 4 grades (0 to grade III) by soloway classification. The levels of serum I CTP and serum BSP were measured by ELISA. The bone metastasis was evaluated again by imaging examination after 6-month follow-up. Results: The levels of serum I CTP and BSP in patients with bone metastasis were significantly higher than those in the patients without bone metastasis and in 30 healthy control group (P<0.05). With the increase of the number of metastatic lesions in the bone metastasis group, the serum levels of I CTP and BSP were increased gradually, and they were positively correlated with the progression of the disease (P<0.01). According to the analysis of receiver operating curve (ROC), the cut-off value, sensitivity and specificity in the diagnosis of tumor bone metastasis were 18 U/L, 85.2%, 98.9% for I CTP, and 2.8 g/L, 87.9%, 99.1% for BSP, respectively. Area under the curve (AUC) was 0.967 for I CTP, and 0.976 for BSP. Among the 52 patients without bone metastasis, 14 were found to have new metastasis during the follow-up. The levels of I CTP and BSP in patients with both new and old bone metastasis were significantly higher than those in the patients without bone metastasis (P<0.05). Conclusion: The serum I CTP and BSP are important biomarkers for diagnosis of bone metastasis, and the increase of their levels can be regarded as risk factors for bone metastasis.