Recent data suggest that angiogenesis in the bone marrow (BM) is augmented and associated with growth of neoplastic cells in various hematological malignancies. Systemic mastocytosis (SM) is a neoplasm affecting multilineage and mast cell (MC)-committed hemopoietic progenitors. In the present study, we have assessed the BM microvessel density (MVD) by CD34 immunohistochemistry in 21 patients with SM, 5 with cutaneous mastocytosis (no BM infiltrates), and 5 control cases (normal BM). The median BM MVD was significantly higher in SM compared to cutaneous mastocytosis or controls (P < 0.05). In addition, a significant correlation (r = 0.74) between the BM MVD and grade of MC infiltration (percent tryptase(+) BM infiltrates) was found in SM. Moreover, the MVD was higher in MC infiltrates compared to the nonaffected adjacent marrow (P < 0.05). Immunohistochemical staining revealed expression of vascular endothelial growth factor in MC infiltrates. The notion that SM is associated with increased BM angiogenesis and vascular endothelial growth factor expression may have implications for the biology of disease and development of new treatment strategies.