Introduction: Determining whether patients with chronic symptoms attributed to Lyme disease (LD) actually have LD or another condition has been a recurring issue since the 1990s. Methods: We evaluated symptomatic patients presenting at a Parisian university hospital from January 2014 to December 2017 for suspected LD using a holistic approach, including presumptive treatment. These patients were classified as having confirmed LD if they met four criteria (except in cases of erythema migrans, where a single criterion was sufficient) and as having possible LD if they met three criteria, including a clinical response to presumptive treatment. Patients with confirmed LB were compared to those diagnosed with other diseases. Results: Among the 301 patients included (183 men, 118 women, median age 50 years), 275 (91%) had been exposed to tick bites and 165 (54%) had been bitten by a tick. At the initial consultation, 151 (50%) had already been treated with a median of 1 (1–22) course of antimicrobial therapy, lasting 34 (28–730) days. The median number of symptomatic organs was 3 per patient (1–12), with a median symptom duration of 16 (1–68) months. The median number of signs was 0 (0–2). ELISA serology was positive in 84/295 (28%) patients for IgM and 86/295 (29%) for IgG; Western blot was positive in 21/191 (11%) patients for IgM and in 50/191 (26%) for IgG. Presumptive treatment following initial presentation failed in 46/88 patients (52%). Overall, presumptive treatment failed in 181/223 (81%) patients. The diagnosis of LB was confirmed in 29 patients (10%) and was considered possible in 9 (3%). Among the 243 patients with a diagnosis other than LB, the primary conditions were of psychological, rheumatological, neurological, or other origin in 76 (31%), 48 (20%), 37 (15%), and 82 (34%) individuals, respectively. Patients with conditions other than BL were significantly younger, had more symptoms, a longer duration of illness, fewer objective clinical signs, and were less frequently seropositive for BL. Conclusion: Overdiagnosis and overtreatment of BL are significant in our study, consistent with two other French studies. Health authorities in our country should address this concerning issue, particularly in light of the need for appropriate antibiotic use.