Granulomatous cheilitis, characterized by persistent inflammation of the lips and a granulomatous histology, is sometimes associated with Crohn's disease and is a therapeutic challenge. Reported evidence indicates treatment with an anti-TNF agent (mainly infliximab) is the most recommended therapeutic option after failure of conventional treatments. The clinical case reported the effectiveness of ustekinumab, a monoclonal antibody against interleukins 12/23, to induce the remission of severe and recurrent granulomatous cheilitis in a patient with Crohn's disease.