Background: Erythema migrans (EM) is the hallmark manifestation of the Lyme borreliosis (LB), and therefore its presence and recognition are sufficient to make a diagnosis and to start proper antibiotic treatment to attempt to eradicate the infection. Methods: In this study we compared the clinical data of 439 patients who presented an EM either according to the diagnostic modality through physical assessment or through telemedicine. Conclusions: Our data clearly show that telemedicine for EM diagnosis is useful as it enables prompt administration of appropriate antibiotic therapy, which is critical to avoid complications, especially for neurologic and articular entities. Therefore, telemedicine is a tool that could be adopted for the diagnosis of Lyme disease both by specialized centers but also by general practitioners.