There is emerging evidence that Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) has a central role in the pathogenesis of Kaposi's sarcoma (KS). The occurrence of HHV-8 in classical KS biopsies is reported irrespective of its clinical stage (patch, plaque, nodular). HHV-8 was detected in 25 of 28 formalin-fixed paraffin-embedded classical KS samples by nested polymerase chain reaction. In addition, in six patients multiple tumors were available (n = 21). Single-strand conformation polymorphism (SSCP) analysis of the amplicons showed uniform SSCP pattern of samples belonging to the same patient regardless of whether the KS was multiplex or developed again years after the first excision. Most of the SSCP patterns were confirmed by further sequence analysis. The presence of the same sequence variant of HHV-8 in various samples of the same patient supports the clonal origin of classical Kaposi's sarcoma.