Chronic rhinosinusitis (CRS) is a heterogenic disease. The effects of heterogeneity on treatment outcome are not very clear. Authors used clinical features such as endoscopic findings scores and full blood count findings in addition to analysis of 35 molecular markers. A total of 246 patients were analysed; 184 of them had polyps. Out of 67 variables, authors managed to group the patients into seven clusters by performing principal component analysis. The seven clusters were different in characteristics such as age, sex, presence of polyps, severity of disease, biopsy findings and treatment outcome. In patients with nasal polyps, those with eosinophilic or neutrophilic inflammation had severe and difficult to treat disease as opposed to those without such inflammation. Additionally, the presence of interleukin 10 or IgE was associated with difficult to treat CRS. However, such correlations were not universal across the seven clusters of patients. Finally, smoking did not appear to negatively affect surgical outcome. This is an interesting study, which is not without limitations such as subjective choice of variables, tertiary centre specimen and being a single centre study. Even with these limitations, the study shed some light on potential causes of treatment failures. It might be beneficial to investigate patients who fail aggressive medical and surgical treatment using clustering criteria in order to direct any further treatment and to counsel the patient.