The perivascular niche regulates breast tumor dormancy. Dormant breast tumor cells (DTCs) reside on microvascular endothelium in distant tissues. The study shows that DTCs remain dormant in the perivascular niche of lung, bone marrow, and brain. Organotypic microvascular niches demonstrate that endothelial cells (ECs) induce and sustain BCC quiescence. Thrombospondin-1 (TSP-1), an endothelium-derived tumor suppressor, is deposited around mature endothelium and is essential for maintaining DTC dormancy. TSP-1 is reduced near sprouting neovascularization, which allows tumors to escape growth regulation. Time-lapse analysis shows that sprouting vessels not only permit but accelerate BCC outgrowth. Active TGF-β1 and periostin (POSTN) are enriched at neovascular tips, promoting tumor growth. The study reveals that stable microvasculature constitutes a 'dormant niche,' whereas sprouting neovascularization sparks micrometastatic outgrowth. The findings suggest that preserving vascular homeostasis is critical to maintaining DTC dormancy. The study also identifies TSP-1 as an angiocrine tumor suppressor and highlights the role of neovascular tips in promoting tumor growth. These findings provide insights into the regulation of tumor dormancy and relapse, with potential therapeutic implications for preventing metastatic relapse. The study underscores the importance of the perivascular niche in tumor biology and highlights the need for therapies that target the microenvironment to maintain dormancy or selectively kill dormant cells.The perivascular niche regulates breast tumor dormancy. Dormant breast tumor cells (DTCs) reside on microvascular endothelium in distant tissues. The study shows that DTCs remain dormant in the perivascular niche of lung, bone marrow, and brain. Organotypic microvascular niches demonstrate that endothelial cells (ECs) induce and sustain BCC quiescence. Thrombospondin-1 (TSP-1), an endothelium-derived tumor suppressor, is deposited around mature endothelium and is essential for maintaining DTC dormancy. TSP-1 is reduced near sprouting neovascularization, which allows tumors to escape growth regulation. Time-lapse analysis shows that sprouting vessels not only permit but accelerate BCC outgrowth. Active TGF-β1 and periostin (POSTN) are enriched at neovascular tips, promoting tumor growth. The study reveals that stable microvasculature constitutes a 'dormant niche,' whereas sprouting neovascularization sparks micrometastatic outgrowth. The findings suggest that preserving vascular homeostasis is critical to maintaining DTC dormancy. The study also identifies TSP-1 as an angiocrine tumor suppressor and highlights the role of neovascular tips in promoting tumor growth. These findings provide insights into the regulation of tumor dormancy and relapse, with potential therapeutic implications for preventing metastatic relapse. The study underscores the importance of the perivascular niche in tumor biology and highlights the need for therapies that target the microenvironment to maintain dormancy or selectively kill dormant cells.