Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson Syndrome (SJS) are severe and rare allergic reactions, with an incidence of 1–10 cases per million people per year, differing only by the percentage of body surface area affected. Symptoms develop 4–28 days after exposure to the causative agent, and mortality can reach 50%. Early recognition of the clinical picture and discontinuation of the offending drug are fundamental for better outcomes. (1) JWRMA, a 31 year old mixed-race woman, previously healthy, with no known allergies, was diagnosed with axillary folliculitis and treated with sulfamethoxazole/trimethoprim (SMX/TMP) 800/160 mg every 12 h for 14 days. On the 14th day, she showed improvement of folliculitis but sought medical care with sore throat, malaise, and conjunctival hyperemia, being diagnosed with tonsillitis and treated with NSAID, ceftriaxone, and hydrocortisone, and discharged with amoxicillin/clavulanate. Within 24 hours she developed diffuse skin lesions (60% of body surface), exfoliative with crusts and blisters, including oral cavity, face, back, chest, genital area, and limbs. She evolved with superficial skin necrosis, with partial preservation of lower limbs. During hospitalization, there was a suspected but unconfirmed intestinal mucosal lesion. She received pulse therapy with methylprednisolone. No hemodynamic instability was observed, but she developed secondary bacterial infection by MRSA, isolated in two blood cultures and one urine culture, successfully treated with vancomycin. TEN is characterized by mucosal erosion, necrosis, and detachment of the epidermis involving more than 30% of body surface. (2) It can occur in any patient, most commonly drug-induced, with allopurinol being the most frequent cause. Antimicrobials are also frequent agents, mainly SMX/TMP and penicillins. (1) The described case shows a typical presentation and favorable outcome, despite the high body surface involvement and MRSA bacteremia. Attention should be given to antimicrobial use, such as prolonged SMX/TMP therapy (14 days for folliculitis) and unnecessary use of ceftriaxone and amoxicillin/clavulanate at the second visit when early manifestations of the disease were already present, totaling three inappropriate prescriptions of antimicrobials most commonly associated with TEN. Rational antimicrobial use plays a fundamental role not only in controlling bacterial resistance but also in preventing diseases and serious adverse events such as TEN.