Bone metastases are a frequent complication of advanced cancer. Interactions between cancer cells and marrow stromal cells and bone turnover mechanisms are crucial in metastases growth and the pathogenesis of bone damage. Metastatic tumour cells stimulate the bone remodelling and indirectly induce the osteocytes to release several growth factors that promote the proliferation of stromal, haematopoietic and neoplastic cells in a sort of vicious circle. Histological examination of bone metastasis of known origin is performed usually to define prognostic and/or predictive markers for target cancer therapy; in the 10–30% of patients in which the primary tumour is not identified, the histologic findings derived from bone biopsy could be diagnostic by morphological or immunohistochemical assessment of the neoplastic tissue.