The diagnosis of SJS is made clinically, based on the characteristic prodrome of a respiratory illness followed by mucocutaneous necrosis involving at least two mucous membranes. Patients with widespread cutaneous necrosis can be difficult to classify, leading to confusion when trying to separate SJS from TEN, especially since the same factors can precipitate both. All forms of SJS have overlapping features with TEN, but most consider the condition to be SJS if two or more mucosal sites are involved. To distinguish SJS from EM, a skin biopsy showing extensive areas of epidermal necrosis can be helpful, as this should only be seen in SJS and TEN, but not in EM.

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