OBJECTIVE: To present a case of an inverted nasal papilloma originating in a rare location i.e., the sphenoid sinus. CASE REPORT: L. F. D. C, a 56-year-old woman, presented at our outpatient clinic with complaints of a frontal headache, occasional otalgia worsened by elevating the head, and recent forgetfulness. Magnetic resonance imaging (MRI) of the head revealed a lesion filling and expanding in both sphenoid sinuses, extending to the posterior ethmoidal cells and the sphenoethmoidal recess. Sinus CT showed an opacified sphenoid sinus with apparent bony integrity. The patient underwent a sphenoidotomy through a transnasal endoscopic approach. A bleeding, papillomatous lesion was identified inside the sphenoid sinus. A biopsy was performed and a fragment of tissue was sent for frozen section analysis. Histopathology suggested inverted papilloma. A complete resection of the lesion was achieved. The patient has been followed-up in the Head and Neck outpatient Clinic, and up to 50 days after surgery, no signs of recurrence have been detected using a flexible nasofibroscope. However, whether this single surgery will be sufficient therapy for our patient in the years to come remains to be seen. Comments: Inverted papilloma is a rare, benign tumor of the nasal fossa. Only 5% of the cases demonstrate exclusive sinus involvement. Although considered a benign lesion, the tumor has a potentially invasive nature and an associated malignancy rate of 7-15%. The nonspecific clinical presentation makes this tumor a diagnostic and therapeutic challenge for otolaryngologists. Close follow-up is required in order to detect possible recurrences or malignant transformation.