Background: Isolated polypoid changes of the middle turbinate were recently reported as having a high association with inhalant allergy. A more advanced manifestation of this association may present as polypoid changes of the entire central sinonasal compartment (i.e., the middle and superior turbinates, and the posterosuperior nasal septum), while the lateral sinus mucosa remains relatively normal. Objective: To introduce and describe this newly recognized variant of chronic rhinosinusitis (CRS), termed central compartment atopic disease (CCAD). Methods: A case series of 15 patients from two institutions who presented with sinonasal symptoms and demonstrated central compartment polypoid mucosal changes on computed tomography (CT). The endoscopic appearance of central compartment edema was assessed. Allergy status was determined by skin or serum in vitro testing. Results: The mean - standard deviation patient age was 42.4 ± 14.8 years, and 47% of the patients were women. All 15 patients had a diagnosis of allergic rhinitis symptomatically, and those who underwent allergy assessment (14/15) tested positive. All the patients had central compartment polypoid edema on endoscopy and central nasal soft-tissue thickening with peripheral clearing on CT. Even with more severe sinus disease, a central focus of inflammatory change existed. Conclusion: CCAD may represent a local inhalant allergy process that affects the central nasal structures of ethmoid origin. Although inhalant allergy changes mainly appear within the nasal cavity, medial-to-lateral progression to involve the sinuses can occur as a simple obstructive phenomenon. This is a pattern of CRS distinct from the more diffuse sinonasal inflammatory disease and likely requires allergy management as a core component.