The role of angiogenesis in neoplastic disorders is supported by the evidence that tumor growth beyond a certain size requires induction of new blood vessels. The extent of tumor-associated angiogenesis, measured as microvessel density (MVD), has shown to correlate with aggressiveness and the prognostic outcome in several malignant neoplasms. Few data have been reported on the angiogenic response in lymphoproliferative diseases. In this study, the MVD has been assessed in benign and malignant primary cutaneous B-cell lymphoproliferative disorders. MVD was determined in formaldehyde-fixed, paraffin-embedded specimens of primary cutaneous B-cell lymphomas (CBCL; n = 18) and cutaneous B-cell pseudolymphomas (B-PSL; n = 22) according to previously described protocols but was performed using computer-aided microscopic morphometry. The endothelial cells of microvessels were identified by immunohistochemical staining for factor VIII-related antigen and CD31. The MVD was 99 dots/mm2 for CBCL and 68 dots/mm2 for PSL, and a MVD of 115 dots/mm2 for CBCL and 73 dots/mm2 for PSL by using an antibody against factor VIII-related antigen and CD31 antigen, respectively. Univariate analysis revealed statistically highly significant differences in MVD between CBCL and B-PSL (P = 0.0036 with staining for factor VIII-related antigen and P = 0.0002 with staining for CD31 antigen). This study analyzes for the first time the angiogenic response in CBCL compared with that of B-PSL and demonstrates that MVD discriminates between CBCL and B-PSL. However, because of an overlap in the ranges of MVD in CBCL and PSL, the MVD is not useful as a diagnostic tool in individual cases.