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Using tissue clearing and three-dimensional (3D) light sheet fluorescence microscopy, we located enhanced green fluorescent protein\u2013positive cancer cells and small clusters in intact bones and quantified their size and spatial distribution. We detected early bone lesions using in vivo microcomputed tomography (microCT)\u2013based time-lapse morphometry and revealed altered bone (re)modeling in the absence of detectable lesions. With a new microCT image analysis tool, we tracked the growth of early lesions over time. We showed that cancer cells home in all bone compartments, while osteolytic lesions are only detected in the metaphysis, a region of high (re)modeling. Our study suggests that higher rates of (re)modeling act as a driver of lesion formation during early metastasis.<\/jats:p>","DOI":"10.1126\/sciadv.adj0975","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T13:58:22Z","timestamp":1708523902000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":20,"title":["From breast cancer cell homing to the onset of early bone metastasis: The role of bone (re)modeling in early lesion formation"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-3863","authenticated-orcid":true,"given":"Sarah A. 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