Rashes and skin lesions are a common reason for patient visits to emergency departments and physicians’ offices. The differential diagnosis includes a variety of infectious and non-infectious diseases, some of which can be life-threatening. The aim of this retrospective study was to evaluate the quantity and type of skin lesions among outpatients and inpatients at a tertiary care university-affiliated teaching hospital for infectious diseases over a three-year period to assess disease burden and physicians’ experience in diagnosing skin lesions. Diagnoses (by ICD-10 codes) were classified into three groups: infectious diseases that include skin lesions, non-infectious skin lesions and undiagnosed skin lesions. During the observed period, out of the total of 142,416 outpatients, 14.8% presented with some form of skin lesion. Among them, 68% had skin lesions inherent to infectious disease, 10.8% suffered from non-infectious skin lesions and 21.2% remained with undiagnosed skin lesions. The most common infectious diagnoses were chickenpox, herpes zoster and unspecified viral infections characterized by skin and mucous membrane lesions. The most common non-infectious diagnoses were urticaria and atopic dermatitis. Overall, the most common individual diagnosis (ICD-10 code) was “nonspecific skin eruption” (n = 4448, 21.1%), which was followed by chickenpox and herpes zoster. Among the 17,401 patients hospitalized over the observed period, 13.1% had skin lesion as the main reason for hospitalization, almost all (97.5%) of which were infectious in etiology. The most common diagnoses were cellulitis, erysipelas and herpes zoster. The presented data suggest that the burden of diseases presenting with skin lesions is significant in everyday infectious disease practice, but the overwhelming number of undiagnosed patients implies the need for further education in this area.