BACKGROUND Four epidemiologic forms of Kaposi's sarcoma have been described, all of which are associated with the human herpesvirus-8. In western countries, human herpesvirus-8 is more prevalent in homosexual men than in the general population, and anecdotal cases of Kaposi's sarcoma in HIV-negative homosexual men have been reported. METHODS We included HIV-negative homosexual and bisexual male patients with histologically proven Kaposi's sarcoma in a retrospective study. Clinical data were collected using a standardized form. Risk factors for human herpesvirus-8 infection and for the development of Kaposi's sarcoma were systematically recorded. RESULTS Between 1995 and 2007, 28 men met the defined inclusion criteria. Mean age at first symptoms of Kaposi's sarcoma was 53 years. Clinical presentation resembled classical Kaposi's sarcoma, with limited disease in most patients. No cellular or humoral immunodeficiency was observed. Serologic tests for human herpesvirus-8 (latent immunofluorescence assay) were positive in 88% of patients, and only two patients displayed human herpesvirus-8 viremia at the time of Kaposi's sarcoma diagnosis. Three patients developed lymphoproliferative disorders (Castleman disease, follicular lymphoma and Burkitt lymphoma). In this population, alpha-interferon was well tolerated and gave a complete response, but most patients require only local treatment, if any. CONCLUSIONS Kaposi's sarcoma may develop in homosexual or bisexual men without HIV infection. This type of Kaposi's sarcoma has clinical features in common with classical Kaposi's sarcoma but occurs in younger patients. Its prognosis is good, as Kaposi's sarcoma is generally limited, but clinicians should be aware of the association with lymphoproliferative diseases, which may affect prognosis.