The risk factors for predicting bone metastases in patients with breast cancer are still controversial. Here, a total of 2133 patients with breast cancer, including 327 with bone metastases (15.33%) and 1806 without bone metastases (84.67%) were retrospective reviewed from January 2005 to December 2015. The spine was found to be the most common site for bone metastases, followed by ribs (57.5%), pelvis (54.1%) and sternum (44.3%). The results indicated that axillary lymph node metastases and the concentrations of CA125, CA153, ALP and hemoglobin were the independent risk factors for bone metastases in patients with breast cancer. The receiver operating characteristics (ROC) curves showed that combined axillary lymph node metastases, high CA153 and ALP, with low hemoglobin were the most accurate biomarkers for predicting bone metastases in breast cancer [area under the curve = 0.900], and the sensitivity and specificity for the prediction were 78.5% and 87.8%, respectively. Therefore, breast cancer patients with more axillary lymph node metastases, high serum concentrations of CA125, CA153, ALP and low level of hemoglobin were closely related to bone metastases. Combined axillary lymph node metastases, CA153, ALP with hemoglobin have the highest predictive accuracy for bone metastases in breast cancer.