Metastasis is one of the major obstacles for breast cancer patients. Limitations of current models demand the development of custom platforms to predict metastatic potential and homing choices of cancer cells. Here, two organ-on-chip platforms, invasion/chemotaxis (IC-chip) and extravasation (EX-chip) were used for the quantitative assessment of invasion and extravasation towards specific tissues. Lung, liver and breast microenvironments were simulated in the chips using tissue-specific cells embedded in matrigel. In the IC-chip, invasive MDA-MB-231, but not noninvasive MCF-7 breast cancer cells invaded into lung and liver microenvironments. In the EX-chip, MDA-MB-231 cells extravasated more into the lung compared to the liver and breast microenvironments. In addition, lung-specific MDA-MB-231 clone invaded and extravasated into the lung microenvironment more efficiently than the bone-specific clone. Both invasion/chemotaxis and extravasation results were in agreement with published clinical data. Collectively, our results show that IC-chip and EX-chip, simulating tissue-specific microenvironments, can distinguish different in vivo metastatic phenotypes, in vitro. Determination of tissue-specific metastatic potential of breast cancer cells is expected to improve diagnosis and help select the ideal therapy.