Toxic epidermal necrolysis (TEN) is a rare complication after allogeneic hematopoietic stem-cell transplantation and carries high mortality rates. Graft-vs-host disease (GVHD) is also a life-threatening complication, and potentially indistinguishable from TEN because of similar clinical symptoms. However, current therapeutic recommendations differ between these two conditions, thereby posing a diagnostic dilemma. The authors, herein, present a complicated postoperative course after bone marrow transplantation with concurrent gastrointestinal and hepatic GVHD, and extensive epidermolytic disease compatible with both severe cutaneous GVHD and TEN. An early consult to a specialized burn service, and prompt transfer to a burn intensive care unit with extensive supportive care and nursing are of paramount importance in the management of immunosuppressed patients with TEN. Better understanding of the pathogenesis of TEN and GVHD after hematopoietic stem-cell transplantation, further treatment strategies, and more advanced diagnostic techniques are still needed to achieve acceptable mortality rates.