Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare immunologic hypersensitivity reaction to stimuli that presents as widespread eruption with mucocutaneous detachment and involvement of other organs. Multiple causes have been noted in literature, including numerous medications. In this report, we present a 52-year-old woman who arrived at the emergency department with a complaint of rash, malaise, and pruritus. She subsequently developed diffuse cutaneous and mucosal detachment. Work-up supported a diagnosis of SJS/TEN secondary to her thyroid replacement therapy, derived from desiccated pig thyroid glands. The patient's natural thyroid medication was discontinued and she responded well to appropriate treatment. This case is unique in that thyroid replacement therapy is not a commonly reported trigger of SJS/TEN. Providers should be aware of the potential for natural thyroid and other animal-derived natural medications to cause adverse reactions such as SJS/TEN.