High serum levels of prolactin increase risk of breast cancer as well as increase metastasis in breast cancer patients. Bone is a preferential site of breast cancer metastasis and breast tumors are known to secrete soluble factors that enhance bone breakdown by stimulating differentiation and maturation of osteoclasts. This project conducted gene and cytokine arrays to elucidate the mechanism by which prolactin contributes to breast cancer-mediated osteoclastogenesis. Here we demonstrate that sonic hedgehog is a prolactin-regulated cytokine in breast cancer cells and is part of the mechanism that induces osteoclast differentiation. Furthermore, sonic hedgehog is expressed more frequently in breast invasive carcinoma tissue than normal tissue, supporting its role in tumor progression and metastasis. This mechanism can lead to the development of novel therapies to help alleviate osteolysis experienced by breast cancer patients.