Mast cells may participate in tumor angiogenesis through the release of angiogenic cytokines from their secretory granules. To gain additional insight into the role of mast cells in bone marrow angiogenesis, we performed a semiquantitative measurement of bone marrow microvessel density in 52 consecutive adult patients with systemic mast cell disease (SMCD). The results were examined for potential correlations with mast cell expression of angiogenic cytokines and with other histologic features of the bone marrow. Standard immunohistochemical methods were used to visualize bone marrow microvessels (CD34 staining) and mast cell expression of transforming growth factor-beta, basic fibroblast growth factor, and their respective receptors. An increase in microvessel density was demonstrated in 32 of the 52 patients (62%) with SMCD, and the degree of bone marrow angiogenesis did not correlate with either the mast cell expression pattern of the study cytokines or the presence (23 patients) or absence (29 patients) of an associated hematologic disorder. In the 29 patients without an associated hematologic disorder, microvessel density was correlated significantly with the presence of an abnormal pattern of hematopoiesis but not with the degree of bone marrow involvement by mast cells. Furthermore, areas occupied by mast cell lesions were often devoid of neovascularization. We conclude that bone marrow angiogenesis characterizes a percentage of patients with SMCD and that the pathogenesis may not necessarily be linked to the mast cells themselves.