Lyell syndrome is an idiosyncratic reaction to drug treatment associated with high mortality due to difficulty in the diagnosis and lack of treatment with proven efficacy. We present the case of a patient treated with antibiotics who developed an exantema-like eruption, diagnosed as Lyell syndrome. The warning signs are represented by a diffuse exantema-like erythema generally associated with fever, large and soft bullae, resembling pemfigo, with subsequent transformation into diffuse erosions following detachment of the epidermis. Skin biopsy is decisive for a correct diagnosis. Negative direct and indirect immunostain, and negative Tzank cytodiagnostic test, associated with histologic findings consistent with "epidermic necrosis with diffuse vacuolar basal stratum degeneration", allow a rapid diagnosis of Lyell syndrome. In our patient, aggressive treatment did not obtain the positive results reported in the literature, possibly due to the advanced stage of the disease.