The objective of this retrospective study is to present a large series of patients with sphenoid sinus fungus ball (SSFB) and describe clinical manifestations, diagnostic workup, surgical treatment, and eventual complications of this disease. We included patients operated on for this disease over a 14-year period. All patients benefited from mid-to-long-term follow-up. There were 28 patients (18 females, 10 males, mean age 64 years). Main symptoms were posterior rhinorrhea and headache. Less common symptoms were alteration of vision or ocular mobility and cacosmia. Preoperative diagnosis was based on nasal endoscopy and CT scanning. MRI was performed in case of suspicion of a tumor, an intraorbital or intracranial invasion. Treatment consisted in endoscopic transnasal or transethmoidal sphenoidotomy with removal of the fungus ball. Specimens were sent to pathology and mycology to confirm diagnosis. Postoperative complications consisted of two cases of epistaxis and two other cases of bacterial superinfection of the operated sphenoid cavity. No recurrence of the fungus ball was seen after a mean follow-up of 13 months. To conclude, SSFB is a relatively uncommon entity, usually due to Aspergillus infection. Although not invasive, if left untreated, it can lead to long-term serious complications. Preoperative nasal endoscopic examination and CT scan are the standard tools for diagnosis. Endoscopic sphenoidotomy with removal of the fungus ball is the current treatment because it has proven effective and has a low morbidity and recurrence rate.