Breast cancer is now the most frequently diagnosed malignant tumor and the second leading cause of cancer-related deaths among women worldwide. More than 90% of breast cancer patients was died from the metastases at distant site rather than the primary tumor. Strategies targeting the primary tumor such as early diagnosis by screening, improved surgical techniques and implementation of adjuvant therapies have markedly improved the survival of primary breast cancer, however, the systemic treatments to prevent metastasis are less effective. Bone is the most common distant site to which the breast cancer metastasizes, and the percentage of bone metastasis reached about 80%-90%. Serious complications caused by the bone metastasis of breast cancer such as bone destruction and associated bone pain, fracture, hypercalcemia, and paralysis due to spinal cord compression were occurred and were incurable. Thus, it is very important to understand the molecular mechanisms of bone metastasis of breast cancer and then find the effective targeted drug therapy. Although the molecular mechanism of bone metastasis of breast cancer is of the highest importance, it has not yet been fully cleared. More than a century ago, Stephen Paget proposed the “seed and soil” theory, that the tumor cells was the seeds, and the bone microenvironment was the soil, the microenvironment of bone tissue may serve as fertile soil on which the cancer cells may grow. This notion has been widely accepted since then and remains the basic principle in the field of cancer metastasis even to the present time. The “Homing hypothesis” suggested that the bone metastasis of breast cancer was due to the tumor cells specifically to bone settlers and homing, the specific types of cancer cells was acted on different organs by chemokines. Although the two hypotheses mentioned above have been accepted, there were still some other factors which influenced the bone metastasis. The process of bone metastasis of breast cancer was complex and was interrelated with many cytokines, growth factors and molecular signaling pathways. Breast cancer is frequently associated with osteolysis. Almost all patients dying of breast cancer or with advanced breast cancer have bone metastases, and these are almost always destructive in nature. This osteolytic lesion could be contributed to the increased osteoclastic bone resorption. So far, the molecule mechanisms of the interaction between the breast cancer cell and bone marrow microenvironment have been explored by many researchers, and in animal models, some agents have also demonstrated having therapeutic effect for bone metastasis in breast cancer by inhibiting the responsible mechanisms. However, breast cancer bone metastasis is a complex process in which each stage are affecting each other, there is still no specific pharmacologic agent available for preventing or reversing bone metastasis in breast cancer patients. Thus, further efforts should be made on how to build the models of bone metastasis which can be used to incorporate all of those affecting factors mentioned above, and how can all the complex interactions in the bone microenvironment be blocked to treat breast cancer bone metastasis. With the development of animal models, molecular biology and gene chip technology, we believe that the molecule mechanism of bone metastasis will be further understood, and then the new targeting drug will be found to cure the bone metastasis in breast cancer. Media Contact: Stella Managing Editor Journal of Orthopedic Oncology. Email: orthooncol@emedscience.org What’s App: +1-947-333-4405