Tenascin-C (TN) is an extracellular matrix glycoprotein expressed during embryogenesis. Its distribution is restricted in normal adult tissues and is upregulated in tumors and inflammatory conditions. Twenty-five specimens were studied, including 7 reactive vascular lesions (6 cases of granulation tissue and 1 case of bacillary angiomatosis), and 18 vascular tumors (6 angiosarcomas, 7 hemangioendotheliomas, and 5 AIDS-related nodular type Kaposi's sarcomas). Formalin fixed-paraffin-embedded tissues were stained with monoclonal antibody to TN (DAKO) and with MIB-1 (AMAC). Heterogeneous expression of TN immunoreactivity was seen in all cases, with a diffuse pattern in bacillary angiomatosis and most granulation tissue cases and a focal pattern in angiosarcoma and most hemangioendothelioma cases. Kaposi's sarcoma cases showed both a focal and diffuse pattern of distribution. In most cases proliferation indices (PI) did not correlate with TN expression. Electron microscopy demonstrated active angiogenesis in bacillary angiomatosis and granulation tissue and vasculogenesis in angiosarcoma and hemangioendothelioma. The study demonstrated positive TN expression in reactive lesions with angiogenesis (granulation tissue and bacillary angiomatosis) and neoplastic lesions showing vasculogenesis (angiosarcoma and hemangioendothelioma), although with a different pattern of distribution. These results suggest that TN might be an important extracellular matrix glycoprotein in angiogenesis and vasculogenesis.