Background: Kaposi’s sarcoma (KS) accounts for more than 5% of malignancies in immunosuppressed organ transplant patients (OKS). A new herpesvirus (HHV-8) was identified with high prevalence in biopsy specimens of AIDS-KS, endemic KS, and classic KS and in OKS. KS has also been associated with other underlying diseases in patients treated with corticosteroids, but this subset of KS has been reported to contain HHV-8 in only a few case reports. Objective: In this larger study, we determined the prevalence of HHV-8 in seven patients of Jewish origin in whom KS developed during immunosuppressive therapy for different primary diseases (ISKS). Methods: The study included HHV-8 DNA detection by polymerase chain reaction (PCR) coupled with Southern blot and sequence analysis as well as by in situ hybridization. Results: HHV-8 sequences were detected by PCR with confirmation by Southern blot and sequence analysis in 100% of the ISKS samples. Direct sequencing revealed several previously unknown base changes within the 208 bp region from open reading frame 26 (ORF26₂₀₈ ) of HHV-8 in ISKS. Conclusion: Ours is the largest known study describing the presence of HHV-8 in iatrogenic KS from immunosuppressed nontransplant patients and provides data of previously unknown sequence variations within the ORF26 of HHV-8 DNA. (J Am Acad Dermatol 1998;38:429-37.)