Toxic epidermal necrolysis (TEN), also known as Lyell’s syndrome, is a life-threatening disease with common development of large wounds. Thus, affected patients are usually treated in specialized centers. Herein, we present a case of TEN in a patient infected with human immunodeficiency virus with the additional, unexpected diagnosis of dengue fever. In this context, we discuss cause, diagnosis, pathology, and treatment of TEN and highlight the role of rare and unexpected findings, as in this case an additional tropical virus infection. We underpin the importance of an interdisciplinary approach involving dermatologists, ophthalmologists, intensive care physicians, burn specialists and various other departments and emphasize the challenge of TEN treatment, especially if rare pathological findings occur.