The staining pattern of monoclonal antibody anti-HPCA-1 (CD-34) was studied in 95 cases of benign and malignant cutaneous vascular proliferations and compared with other vascular endothelium-associated antigenic markers in paraffin-embedded tissues. The proliferating vessels in 22 cutaneous capillary hemangiomas, 8 lobular capillary hemangiomas, and 1 case of papillary intravascular endothelial hyperplasia stained strongly positively for anti-HPCA-1, and the intensity of the reaction was paralleled by that of factor VIII-related antigen (FVIII), Ulex europaeus lectin-1 (UEA), and vimentin (VIM). The vessels in 10 cases of granulation tissue, 6 cases of cavernous hemangioma, 6 cases of angiokeratoma, 5 cases of angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma), and 3 cases of bacillary angiomatosis showed a lack of reactivity with anti-HPCA-1 and staining of variable intensity with the other markers. Twenty cases of Kaposi's sarcoma (seven patch, five plaque, eight nodular stage) showed strong labeling with anti-HPCA-1 in small, well-formed vessels scattered among the spindle-cell proliferation, and four of these cases showed focal positivity of scattered spindle cells. Nine cases of cutaneous angiosarcoma, two cases of low-grade epithelioid angiosarcoma, and one case of spindle-cell hemangioendothelioma were negative for anti-HPCA-1 and showed variable reactivity for FVIII and UEA; all cases stained strongly positively for VIM. The results of this study indicate that although anti-HPCA-1 shows a high sensitivity for the staining of normal vascular endothelium, its specificity may be restricted to mature, well-formed vessels, therefore rendering its discriminatory value very limited for the identification of poorly differentiated vascular endothelial neoplasms.