The diagnostic approach to febrile skin eruptions in adults requires a systematic methodology, combining an accurate history with careful clinical evaluation. The most frequent etiologies of febrile exanthem in the immunocompetent patient can be categorized as infectious (viral or bacterial) or non-infectious (toxidermia, connectivitis or vasculitis). Mononucleosis, primary HIV infection, secondary syphilis, disseminated gonococcemia and exanthematous drug eruption, are mentioned in detail in this article due to the difficulty of establishing a diagnosis in ambulatory medicine. A clinical vignette is presented to illustrate the reasoning in primary care, with recourse to further investigations depending on the clinical course.