Background Inverted papilloma (IP) is a benign, but locally aggressive neoplasm of the nasal cavity and paranasal sinuses. The mainstay of treatment of IP is surgical resection, but high rates of tumor recurrence have been reported. Cyclo-oxygenase-2 (COX-2) has been found to be overexpressed in many tumors and has been used successfully as a therapeutic target. The goal of this study is to highlight COX-2 expression in IP. Methods Immunohistochemistry for COX-2 was performed on IP samples obtained during surgical resection between January 2012 and June 2013. The intensity of staining was evaluated by 2 head and neck pathologists blinded to the clinical features and outcomes. A positive stain was defined as having 10% or more of tumor cells exhibiting immunoreactivity. Results The study includes 13 tumor samples from 7 females and 6 males. Mean age was 54.5 (range, 18-81) years. Tumor locations included: nasal septum (1), ethmoid (3), sphenoid (4), and maxillary (5) sinuses. No tumors demonstrated malignancy or dysplasia. Five (38%) of the 13 IP samples stained strongly positive for COX-2, and 3 of 13 (23%) stained weakly positive. There were no clinical differences in patients that stained strongly or weakly for COX-2. Conclusion COX-2 overexpression was identified in 62% of cases of IP in this study, and strongly positive in 38% of cases. Larger studies are necessary to identify the true incidence of COX-2 expression for this tumor. Pharmaceuticals targeting COX-2 may eventually provide an additional therapeutic option for select cases of recurrent or unresectable IP. [ABSTRACT FROM AUTHOR]