This case report describes the first known successful treatment of exfoliative cheilitis with the interleukin-4 receptor alpha antagonist dupilumab in an adult patient. With no response to topical tacrolimus, hydrocortisone, dapsone, crisaborole or systemic doxycycline, low dose isotretinoin, or methotrexate, she had resolution with off-label dupilumab after 4 months of treatment.