Erythema multiforme is an acute, self-limiting, mucocutaneous hypersensitivity reaction characterized by distinctive target lesions. Most cases have been attributed to infection. Erythema multiforme occurs mainly in young adults and is extremely rare during the neonatal period. We report a 25-day-old girl who presented with target skin lesions on both the palms and soles with no other associated symptoms. She had no remarkable maternal, birth, or past medical history. Complete blood count, urinalysis, chest radiography, and herpes simplex virus 1 and 2 immunoglobulin G (IgG) titers revealed no abnormalities. Pathologic examination showed vacuolar interface change and dyskeratotic cells in the epidermis consistent with erythema multiforme. This unusual case emphasizes the importance of recognizing diagnostic clues in examining patients. Even in the presence of uncharacteristic factors, the typical target lesions of erythema multiforme are distinctive.