Lyme disease is currently a hot topic in France due to a high incidence in some areas. Its clinical polymorphism can lead to misdiagnosis on one hand and to unjustified treatment on the other hand. Clinical symptoms vary considerably according to involved organs (skin, central and/or peripheral nervous system, joints, heart, eyes) and may be limited to or associated with general non-specific signs. Biological exams must be guided by clinical symptoms to help diagnosis and treatment decision according to clinical history, presentation, time of onset and duration of symptoms. However, to date, no serologic test can discriminate between past and active disease. The role of the internist is two-fold: make a diagnosis when faced with general or focal symptoms and avoid inappropriate attribution to Lyme disease of symptoms related to alternate diagnoses.