Bone metastasis is an important factor for determining the appropriate treatment for patients with lung cancer. The cross-linked N-terminal telopeptide of type I collagen (NTx) is a metabolite of type I collagen, the main constituent of the bone matrix. Urinary NTx is recognized as a useful marker of bone metastasis, but the application of serum NTx and its cutoff value for determining bone metastasis from lung cancer have not been characterized. We measured serum NTx by enzyme-linked immunosorbent assay of individuals who underwent staging during hospitalization for initial treatment of lung cancer in our department and compared the NTx levels with the presence of bone metastasis in staging. The study included 166 patients with lung cancer (128 men and 38 women), including 85 adenocarcinoma, 42 squamous cell carcinoma, 32 small-cell carcinoma, and 7 other cancer types. Bone metastasis was present in 73 cases. The average/median serum NTx of bone metastasis (+) and bone metastasis (-) was 27.8/23.8 and 17.1/16.5 nmol bone collagen equivalents/L, respectively. There was an intentional difference with P < 0.001. The cutoff value of the serum NTx level indicating bone metastasis from lung cancer was estimated using the receiver operating characteristics curve. The optimal cutoff value was found to be 22.0 (sensitivity: 61.6%, specificity: 89.2%). The results of univariate and multivariate analysis revealed that the serum NTx levels were significantly related to bone metastasis from lung cancer (P < 0.001). Measurement of serum NTx levels provides a simple diagnostic marker of bone metastasis from lung cancer.