Objective: To review the current South American literature on classic Kaposi's sarcoma (KS) and human herpesvirus 8 (HHV-8), and point the way for studies that still need to be performed. Materials and methods: The authors performed an exhaustive search in LILACS, SCIELO and PUBMED databases for classic KS and HHV-8 in South America. The relevant material was evaluated and reviewed. Results: More than 250 cases have been reported with three big case series (Argentina, Colombia and Peru). The classic KS form seen in Colombia resembles the type of disease seen among African communities; the same unusual presentation with confluent exophytic nodules or eroded lesions has been noticed in Peru. Low rates of HHV-8 antibodies have been found in blood donors from Chile, Argentina and Brazil (3%, 4%, 2.8-7.4%, respectively); whereas high rates of HHV-8 antibodies have been found in Amerindians from Brazil and Ecuador. Five specimens from Argentina were subtyped: (three classic KS and two AIDS KS); the identified strains fell into subtypes A and C. AIDS-related KS specimens from Brazil and Venezuela were subtyped: (43 and nine respectively); analysis grouped them predominantly into subgroups A, B and C. A new HHV-8 subtype E was found endemic in Brazilian and Ecuadorian Amerindians. In French Guiana ten endemic KS and six AIDS-related KS specimens were subtyped; analysis grouped them predominantly into subgroups A, B and C. Conclusion: Classic KS in South America has a very similar clinical presentation but not the same as the classic KS variety described in the Mediterranean. Initial seroprevalence studies performed in the general population and in blood donors showed low seroprevalence of HHV-8, whereas high seroprevalence rates were seen in Amerindian population. The existing serological assays, nonetheless, need to be further refined, and new assays need to be developed. Finally, the key to understanding the precise molecular epidemiology and phylogenetic distribution of HHV-8 in South America would be to perform more subtyping of classic KS cases. © 2005 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.