The discovery of the MAPK pathway mutations in lesions of patients with Langerhans cell histiocytosis (LCH) has made targeted therapy an important therapeutic approach for these patients. Theoretically, the RAF-independent mutation is naturally resistant to allosteric MEK inhibitors. We report a dramatic response to MEK inhibitor trametinib in a case of LCH with mutation, which indicates that trametinib is worth trying in recurrence and refractory LCH patients with . : The authors have confirmed clinical trial registration is not needed for this submission.