Advanced breast cancer commonly spreads to the bones, lungs, liver or brain, and bone is the most common site of breast cancer metastasis. Nearly all patients with advanced breast cancer develop bone metastasis and suffer from serious bone metastasis-associated complications, including chronic pain, fracture, spinal cord compression and hypercalcemia. Metastasis formation in the bone is a complex process that requires cooperative reciprocal interactions between tumor cells and the cellular environment of the bone, which includes osteoclasts and osteoblasts. We have developed a murine bone invasion model of breast cancer, which required a simple surgical technique and mimics the biology of the disease. Osteolytic and/or osteoblastic lesions induced in the tumor-bone interface allowed us to explore cellular and molecular interactions between malignant cells and skeletal tissue in a syngeneic setting. In this review, we will discuss a different animal model that provides a consistent and reproducible platform for investigating the molecular mechanisms underlying tumor-bone interaction and breast cancer-induced osteolytic changes.