Background: Antrochoanal polyp (ACP) is a rare and unique unilateral nasal polyp. In contrast to diffuse primary chronic rhinosinusitis (d-CRS) the inflammatory profile of ACP in the Caucasian population have not been determined. Objective: The purpose of the study is to describe and differentiate the inflammatory features of ACP compared with d-CRS and its phenotypic subgroups and hypertrophic turbinates (HT) in the Caucasian population, and compare the mast and plasma cell marker expression of each pathology. Methods: A retrospective case control study of 96 patients operated on between the years 2005–2017. Nasal biopsies of ACPs, d-CRS and HTs were compared. A comparison of the different phenotypic subgroups of d-CRS was made as well. Demographics, comorbidities, and histologic and immunohistochemical (IHC) staining of mast (CD117) and plasma cell (CD138) receptor antibodies, were compared and analyzed. Results: A total of 96 patients were included, consisting of 40 (41.6%) ACP, 36 (37.5%) d-CRS and 20 (20.8%) HT patients. ACPs displayed a significantly higher level of edema and intramural cysts compared to the other groups. Squamous metaplasia was demonstrated in ACP (27.5%) and d-CRS (25.6%), but not in HT. The ACP group was characterized by neutrophilic predominant infiltrates as opposed to the eosinophilic predominance in the d-CRS group, especially in eosinophilic CRS and central compartment allergic disease. ACP presented lower levels of both mast and plasma cells compared to d-CRS and HT in IHC staining. Conclusions: ACP in the Caucasian population has unique features of cyst formation and edema which is compatible with its clinical presentation. It is characterized by neutrophilic predominant infiltrates and expresses lower levels of mast and plasma cells as demonstrated by IHC.