Erythema Multiforme (EM) is an acute, self limited, immune–mediated condition, most commonly induced by herpes simplex virus (HSV) infection, or by the use of medications, such as phenytoin, sulfonamides, penicillins, and barbiturates. The disease is characterized by targetoid lesions, with concentric color variations, and often are accompanied by erosions or bullae in the genital, ocular, or oral mucosae. EM is clinically characterized by a “minor” form and a “major” form. The clinical course of the disease ranges from exanthematous variant with minimal oral involvement to a progressive, fulminating, severe variant with extensive mucocutaneous epithelial necrosis (Stevens–Johnson syndrome); and toxic epidermal necrolysis. There are no specific diagnostic tests for EM, and the diagnosis is mainly clinically supported, if necessary by biopsy. This article highlights a case report of erythema multiforme in a 26 years old female patient with extensive involvement of oral mucosa.