This study analyzes the ethical aspects of a research program conducted over a decade (1994–2004), coinciding with the enactment of bioethics laws in France. These studies on human T-cell lymphotropic virus type 1 (HTLV-1) were conducted in French Guiana among a specific population, the Maroons. In this population of African origin, this oncogenic retrovirus is highly endemic, and associated T-cell leukemias and lymphomas are relatively common. The Maroons have lived in self-sufficiency along the Maroni River for nearly two centuries. Their “recent” settlement on the French side of the river, as well as a significant influx of immigrants triggered in the 1990s by a civil war in Suriname, explain this population’s low level of education. In this particular context, our investigations have revealed the limitations of the legal framework currently applicable to this type of research. Indeed, several ethical questions have been raised regarding the assessment of benefit, the specifics of participant information and consent, as well as the relevance of individual feedback. The aim of this study is to describe the ethical issues raised in this type of research and to discuss information procedures. This retrospective analysis has enabled us to improve our practices and to consider implementing new tools that facilitate genuine dialogue with the individuals involved. We believe this reflection is essential at a time when ethics is becoming increasingly important in epidemiological research programs.