Bone is the most common site of metastasis of breast cancer, affecting most women with advanced disease. Procollagen type I N-terminal propeptide (P1NP), osteocalcin, CTX, and IL-6 are markers of bone turnover. Our objective was to determine whether serum levels of these proteins have clinical utility as predictors of breast cancer metastasis to bone. Blood was collected before treatment from 164 patients with stage I-III breast cancer from September 2001 to December 2008. Serum levels of P1NP, CTX, IL-6, and OC were measured using an automated immunoassay system. Correlations of the levels of these markers with time to bone metastasis development and with overall survival (OS) rate were assessed using Cox proportional hazards regression analysis and the Kaplan-Meier method. Fifty-five patients with stage I-III disease at the time of blood sample collection subsequently experienced metastasis to bone. A baseline P1NP level of at least 75 ng/mL predicted increased risk of bone metastasis (hazard ratio, 2.7 [95 % confidence interval, 1.2-6.0]; P = 0.031) and a poor OS rate (P = 0.031). Serum P1NP levels at or above 75 ng/mL correlate with a short time to development of bone metastasis and low overall survival in patients with stage I-III breast cancer.