Toxic epidermal necrolysis (TEN) is the most severe and potentially life-threatening cutaneous reaction associated with lamotrigine. The risk of developing TEN during lamotrigine therapy is low and previously reported cases most involved epileptic patients. However, the risk of TEN with combination lamotrigine and valproate is greater than with monotherapy. We present here the emergence of TEN in a 32-year-old bipolar woman who was concomitantly treated with lamotrigine and valproate. The patient developed high fever, pharyngitis, cervical lymphadenopathy, mucosal sloughing, generalized erythematous eruptions and more than 40% epidermal detachment of the total body surface area (TBSA) after we added lamotrigine to her medications of valproate and trazodone. The patient's illness course was protracted and accompanied with hepatitis, pneumonitis and hematologic abnormalities. In the beginning of her illness course, our patient did not respond to antihistamine treatment. However, she made a full recovery without any sequela after she had received systemic corticosteroid and intensive resuscitation. Our case suggests that early use of systemic corticosteroid might be beneficial in treating TEN patients, if there is not any clinical contraindication.