The skeleton is the most common site of breast cancer metastasis. Accumulating evidence indicate that breast cancer cells preferentially disseminate to a specialized niche within the bone marrow for efficient outgrowth, but the specific location of this niche remains controversial. To study the metastatic niche in situ, we established a robust and quick protocol to perform high resolution, deep imaging of mouse and human bone marrow specimens. This technique allows accurate detection of disseminated tumour cells and three-dimensional reconstruction of various bone marrow niche components for quantitative analysis. Using this technique, we identified that disseminated human and murine breast tumour cells preferentially interact with a specialized blood vessel subtype within the marrow. This pattern of breast cancer bone colonisation is independent of animal age and the route of injection. We further demonstrated that depletion of this vessel subtype in aged mice markedly reduced bone metastasis burden in both intracardiac and spontaneous metastasis models. Together, our work proposes that breast tumour cells utilize a unique blood vessel subtype to invade the bone marrow and a targeted approach to modulate these vessels may represent new strategy to control bone metastases.