Abstract Background Florid oral papillomatosis is characterized by its tendency to local recurrence that requires multiple treatments, leading to important functional sequelae. Methods We present 74‐year‐old woman with oral florid papillomatosis (OFP) who refused a new surgical treatment, and was treated with imiquimod 5% in orabase on alternate days for 16 weeks. Treatment was complemented with application of hyaluronic acid gel. Results There were no side effects to the treatment, nor signs of local recurrence, in the treated area at 2 years of follow‐up. Conclusions After reviewing the literature and according to our knowledge, this is the first published case of oral florid papillomatosis treated topically with imiquimod 5% successfully. Topical treatment with imiquimod 5% in orabase may be a valid alternative for patients with recurrent OFP located in the anterior area of the oral cavity who refuse surgical treatment, although we must closely monitor the patient for the possibility of recurrence or malignant degeneration.