AbstractWhile there have been many important advances in the study of Kaposi's sarcoma (KS), it remains both a challenge and an enigma in many ways. Kaposi's original description of “multiple idiopathic hemorrhagic sarcoma[s]” in patients who died within 2–3 years resembles KS in AIDS more than classic KS in elderly men of Italian, Jewish, or Mediterranean lineage, in whom the disease is usually benign. KS had been evident in about one‐third of those with early AIDS, often as its presenting sign, a pattern markedly reduced in recent times since the introduction of highly active anti‐retroviral therapy (HAART). The most important advance has been the convincing etiologic linkage of KS with human herpesvirus 8 (HHV‐8), which is necessary but not sufficient. It has a low prevalence in the general population of the USA and UK, with an intermediate rate in Italy and Greece, and a high one in Uganda. KS risk may be significantly lower in AIDS patients with a history of anti‐herpes therapy. Many aspects of HHV‐8, including its transmission pattern and different genospecies, are being scrutinized. The diagnosis of KS may be difficult. One should be aware of KS clinical variants, including telangiectatic, eccymotic, and keloidal KS. One must consider a number of other disorders, including bacillary angiomatosis. HHV‐8 DNA sequences in dermatofibromas and other tumors should probably not be viewed as representing a marker for KS. Therapeutic options vary for KS. Intralesional and low‐dose outpatient intravenous vinblastine may be valuable, as immunosuppression with KS is not a good idea if it can be avoided. Anti‐herpes virus therapy may have potential for wide use, especially in preventing the development of KS in at risk populations, such as HHV‐8 seropositive individuals undergoing transplantation surgery. J. Surg. Oncol. 2004;87:146–151. © 2004 Wiley‐Liss, Inc.