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breast cancer cells, and their subclones that have previously been isolated from mice and shown to consistently target either bone or lung tissues in vivo, were used, and their spread to the tissues was monitored over 2 weeks. Tissue specific functions were assessed throughout the process of metastatic progression using a combination of assays, and compared against clinical benchmarks.Results: We found that the use of an organs-on-a-chip platform with a vascular barrier was critical to both the maintenance of tissue specific function and to the recapitulation of breast cancer metastasis across both tissues. Additionally, we were able to recreate metastasis-specific processes documented in breast cancer patients, including the multiple stages of the metastatic cascade and osteolytic cycle activation. Finally, we were able to use our fully human and bioengineered integrated multitissue model in combination with organ-specific breast cancer subclones to recreate targeted bone and lung metastases.Conclusions: Breast cancer metastasis is a complicated, dynamic, and clinically important process of cancer that requires new models to enable more impactful study. Our model system offers a variety of advantages: it is entirely human, yet manages to incorporate multiple tissue types, recreate multiple stages of metastatic progression, and capture the organ-specificity of various breast cancer subclones.Legal entity responsible for the study: The authors.