A unique case of IgG4(+) sclerosing disease was diagnosed in the sphenoid sinus, a previously unreported location, and was treated in a novel manner. This study describes the clinical presentation and management of IgG4 sclerosing disease in the paranasal sinuses. A retrospective case review and review of the medical literature were performed. A 38-year-old woman with a 2-year history of constant frontal headaches presented to our clinic. Imaging showed bony destruction of the sphenoid sinus and sellar floor. The patient underwent a right-sided sphenoidotomy with debridement and biopsy. Pathological evaluation showed a dense plasmacytic infiltrate with >150 IgG4(+) cells/high-power field. She was subsequently started on a nasal corticosteroid with improved patency of the sphenoid antrostomy. We report an unusual case of a middle-aged woman who presented with IgG4-sclerosing disease (IGSD) isolated to the sphenoid sinus. Although our knowledge concerning treatment in extrapancreatic organs is lacking, there is evidence that glucocorticoid treatment improves nasal sinus opacification on CT findings (Sato Y, Ohshima K, Ichimura K, et al., Ocular adnexal IgG4-related disease has uniform clinicopathology, Pathol Int 58:465-470, 2008). This case study and literature review adds to the growing literature describing IGSD in the head and neck and more specifically isolated to the sphenoid sinus with preliminary data concerning local control with topical steroids.