Bone is a common site for metastasis in breast cancer; approximately 75% of women with advanced breast cancer will develop bone metastases. Bone metastases associated with breast cancer are predominately osteolytic. Receptor activator of nuclear factor-κB ligand (RANKL) is a key mediator in the vicious cycle of bone destruction in metastatic cancer. Within the bone microenvironment, factors secreted by tumor cells stimulate stromal cells and osteoblasts to express and secrete RANKL, which binds to RANK on the surface of precursor and mature osteoclasts. RANKL is a critical mediator of osteoclast differentiation, function, and survival. The present study aimed to assess the relevance of RANKL to other prognostic factors in breast cancer patients with and without bone metastases. The study was conducted on eighty females who were divided into four groups: group I (n=20) healthy females as a control group, group II (n=20) non-metastatic breast cancer patients, group III a (n=20) breast cancer patients with bone metastases not receiving Bisphosphonates treatment And group III b (n=20) breast cancer patients with bone metastases and were receiving Bisphosphonates treatment. All participants were subjected to a thorough clinical assessment, and estimation of blood levels of fasting glucose, ALT, AST, alkaline phosphatase, urea, creatinine, bilirubin, and RANKL. The serum levels of RANKL showed a significant increase in breast cancer patients (with and without bone metastasis) compared to the control group. Also, a significant increase in RANKL level was found in breast cancer patients with bone metastasis without Bisphosphonates treatment compared to those with Bisphosphonates treatment. Also, a significantly positive correlation was found between RANKL and tumor size. This means that, RANKL may be used as a prognostic marker in breast cancer patients.