BACKGROUND Erythema multiforme (EM) is a complex disease that may have cutaneous and/or mucosal involvement. The severity may range from mild to severe and potentially life threatening. The literature cites many factors including viruses, infections, and medications as causes. This report documents a patient who developed EM secondary to a herpes simplex viral (HSV) infection. METHODS Two weeks following an eruption of herpes labialis, a 20-year-old white female patient developed acutely painful oral and labial ulcers accompanied by target skin lesions. A diagnosis of erythema multiforme (EM) was made. The patient was treated with antivirals, analgesics, and symptomatic therapy. RESULTS Nine days after the onset of symptoms, the oral and cutaneous lesions had started to heal and the patient no longer required pain medication. CONCLUSIONS Although the etiology of EM is still often unknown, infections with herpes simplex virus have been implicated as a possible precipitating factor. This case illustrates the association of the occurrence of EM with an HSV infection.