Background: Tissue eosinophilia in chronic rhinosinusitis (CRS) is a marker of inflammatory disorders recalcitrant to surgical intervention. Eosinophilic chronic rhinosinusitis (ECRS) is traditionally associated with asthma, polyps, aspirin sensitivity, high serum eosinophilia, and elevated immunoglobulin E (IgE). However, patients with ECRS may not present with these associations and there is a need to establish other surrogate markers. The objective of the study was to determine the associations between the histopathology, serology, and clinical characteristics in CRS patients. Methods: A cross-sectional study was undertaken of CRS patients undergoing surgery. Tissue eosinophilia and other pathological features were compared to traditional surrogate features of ECRS, as well as to symptoms, and to radiologic and endoscopic scores. Results: A total of 51 patients were assessed (47% female, mean age 46.6 ± 4.1 years). High tissue eosinophilia (>10 per high-power field [HPF]) was more prominent in polyps (84%) (χ2 = 25.76; p < 0.01) but was also seen in nonpolyp patients (19%). Asthma was not associated with high tissue eosinophilia (p = 0.60), with 43% of nonasthmatics demonstrating high tissue eosinophilia. Serum eosinophilia predicted high tissue eosinophilia at >0.30 × 109/L or 4.4% of leukocytes (sensitivity 52%, specificity 87%, receiver operating characteristic [ROC] p = 0.001), with low negative predictive value. Serum IgE was nonpredictive (p = 0.08). Conclusion: The diagnosis of ECRS has unique prognostic implications. Traditional features of the ECRS phenotype are not necessarily reliable markers for the presence of tissue eosinophilia. Serum eosinophilia may be a good surrogate marker of tissue eosinophilia but of limited use. The routine use of structured histopathology reporting in CRS is suggested, to allow for the diagnosis of ECRS and to identify other prognostic markers.