Between Gomisin-D metastatic tumor cells and the existing neurovasculature. We focused on timepoints as early as 3d after intravascular injection in order to focus on the earliest events in microcolony formation. We found that brain micrometastases in mouse and human tissue utilized vascular Chloroquine Phosphate cooption for growth rather than invading and growing within the neural parenchyma. Vascular cooption can be an alternative to neoangiogenesis and likely acts to deliver blood borne nutrients and oxygen. We propose here that vascular cooption has an additional function for brain metastases; interactions with the pre-existing vessels are required for initial adhesion, proliferation, invasion, and microcolony establishment. We show that the neural parenchyma of the brain cannot substitute in supplying these functions. This work identifies the central role of the vasculature for metastatic growth in the CNS as well as providing insight into the mechanism of adhesive vascular cooption. These novel concepts may allow the development of more effective therapies for brain metastasis. To characterize the vascular association of tumor cells in experimental brain metastasis models, we examined early brain microcolony formation after intracardiac injection of metastatic mouse and human tumor cells. It has been anecdotally noted that microcolonies in experimental brain metastasis assays often tended to grow along preexisting vessels. We established that this pattern occurs with a high frequency and across all cell lines we tested. 4T1-GFP mammary carcinoma cells were found to be intimately associated with the perivascular surface of brain microvessels from the earliest timepoint at 3 d up to 14 d after injection into syngeneic BALB/c mice. This was observed in over 97% of the microcolonies at all timepoints. Similar vascular associations resulted from the intracardiac injection of the human breast carcinoma cell lines MDA-MB-231 and its “brain seeking” variant cell line MDA231BR, the human melanocarcinoma cell line A7 in SCID mice, and the murine melanoma cell line K1735M2 injected into syngeneic C3H/He mice. Brain microcolonies from each of these cell lines examined between 7 and 14 d after injection were associated with vessels in the same pattern consistent with vascular cooption. Interestingly, the “brain seeking” MDA231BR line showed equivalent vascular association and microcolony area as the parental line.