Drug-induced hypersensitivity syndrome (DIHS) is a life-threatening idiosyncratic drug reaction, and an early accurate diagnosis is essential for its treatment. We describe a 14-year-old boy with localization-related epilepsy, who developed severe adverse cutaneous and systemic reactions after 3 weeks of carbamazepine administration. During the course of the clinical symptoms, reactivation of human herpesvirus 6 (HHV-6) was proven by detection of the HHV-6 genome in serum and elevation of HHV-6 immunoglobulin G (IgG). He fulfilled the newly established criteria for DIHS. Among eight identified medications that can precipitate DIHS, four are antiepileptic drugs. Establishing a treatment strategy for DIHS is warranted to improve its outcome. Therefore, it is important to raise awareness of DIHS among epileptologists.