The contribution of the tumor stroma to cancer progression has been increasingly recognized. We had previously shown that in human neuroblastoma tumors orthotopically implanted in immunodeficient mice, stromal-derived matrix metalloproteinase-9 (MMP-9) contributes to the formation of a mature vasculature by promoting pericyte recruitment along endothelial cells. Here we show that MMP-9 is predominantly expressed by bone marrow–derived CD45-positive leukocytes. Using a series of bone marrow transplantation experiments in MMP-9^+/+ and MMP-9^−/− mice xenotransplanted with human neuroblastoma tumors, we show that bone marrow–derived MMP-9 is critical for the recruitment of leukocytes from bone marrow into the tumor stroma and for the integration of bone marrow–derived endothelial cells into the tumor vasculature. Expression of MMP-9 by bone marrow–derived cells in the tumor stroma is also critical for the formation of a mature vasculature and coverage of endothelial cells with pericytes. Furthermore, in primary human neuroblastoma tumor specimens of unfavorable histology, we observed a higher level of tumor infiltration with MMP-9 expressing phagocytic cells and a higher degree of coverage of endothelial cells by pericytes when compared with tumor specimens with a favorable histology. Taken together, the data show that in neuroblastoma, MMP-9 plays a critical role in the recruitment of bone marrow–derived cells to the tumor microenvironment where they positively contribute to angiogenesis and tumor progression.