Microscopic diagnosis of early Kaposi's sarcoma continues to be a challenge to the pathologist, as does the identification of bacillary angiomatosis (BA) which may have a similar appearance. 120 oral Kaposi's sarcoma (KS) biopsies submitted to the UCSF oral pathology service from 1981-1991 were reviewed in order to describe the clinical-pathologic spectrum of these lesions and to search for unrecognized cases of BA. Also, histopathologic features of oral KS were compared to 30 oral pyogenic granulomas, and immunohistochemical stains for endothelium-associated CD34 antigen were done. The diagnosis of KS was confirmed in all biopsies and no cases of BA were found. Histologically, the KS specimens exhibited numerous features that separated them from pyogenic granulomas, and could themselves be divided into two clinical-pathologic subtypes: small, well-delineated macular lesions (31), which were characterized by inconspicuous patches of spindle cells containing ill-defined vascular spaces; and larger, infiltrative nodular lesions (89), which were characterized by spindle cells lining vascular slits and bizarre-shaped vessels. Extravasated RBCs were evident in almost all KS lesions; hemosiderin deposits and hyaline globules were seen in half of each of the small and large lesions. Nuclear atypia was minimal and mitotic activity was slight. Lymphocytes in small lesions added to the difficulty of microscopic interpretation of these incipient lesions. CD34 was expressed on all spindle cells lining vascular spaces in larger lesions and on spindle cells of small, subtle lesions. We conclude that within the spectrum of lesions that are diagnosed as oral KS, two clinical-pathologic types can be identified: macular small spindle-cell lesions and nodular infiltrative vascular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)