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Skeletal bone is an attractive site for secondary tumour growth and is also home to spontaneous primary cancer. Treatment of bone metastasis is focused on limiting the vicious cycle of bone destruction with bisphosphonates or inhibition of receptor activator of nuclear factor-κB ligand (RANKL) with the fully human monoclonal antibody denosumab. The estimated 1 million deaths/year where bone metastasis is present, and the high healthcare costs required for its management, have ignited intensive research into the cellular and molecular pathology of osteolysis, involving interplay between tumour cells, bone-forming osteoblasts and bone-degrading osteoclasts. Compared to bone metastasis, knowledge about the pathology of primary bone cancers is limited. In recent work published in this journal, Engelholmet alprovide a unique insight into how this poorly understood disease manifests and destroys bone. For the first time they have demonstrated that a mouse monoclonal antibody targeting the collagen receptor Endo180 (CD280, MRC2 uPARAP) can prevent osteolysis and bone destruction in a syngeneic model of advanced osteosarcoma. Their convincing findings make an important contribution towards Endo180-based therapy being developed as an option for the treatment of bone cancer amongst other malignancies. © 2015 The Authors.The Journal of Pathologypublished by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.