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Toxic epidermal necrolysis (TEN) or Lyell’s syndrome is a rare but serious potentially fatal autoimmune dermatologic disease. It is characterized by cutaneous damage due to apoptosis of the keratinocytes with consequent dermo-epidermal separation for a >30% extension of the body surface, associated with mucosal lesions. It is due to the activation of the immune system, often following the intake of potentially toxic drugs [antibiotics, antiepileptics, non-steroidal antinflammatory drugs (NSAIDs), allopurinol] or after infection with herpetic viruses or mycoplasma. We describe the case of an 82- year-old man starting therapy of Allopurinol for hyperuricemia. After four days the patient shows an extensive erythematous rash localized to the trunk and upper limbs. The following day the rash also involves the face, tending to the confluence and after another two days, the macules turn into de-epithelized areas because of dermo-epidermal separation and the lesions involve the oral and ocular mucosa, causing dysphagia and difficulty in speaking. He was treated with steroid and antihistamine therapy, suspending the previously undertaken therapy with antibiotic and Allopurinol.