Basic science studies directed at understanding the inflammatory mechanisms in chronic rhinosinusitis (CRS) are increasing, yet their relevance to the underlying disease process is often conflicting and confounded by the enrollment of a heterogeneous CRS population. This review is aimed at exploring the issues affecting the basic science mucosal studies of CRS patients, with special attention to the inclusion criteria for CRS and the control group, and the site from which the mucosal tissue sample is obtained.A common confounding factor is an inadequate documentation of selection criteria for patients, controls, and tissue sites examined. Inconsistent definitions for CRS and for maximum medical therapy, and a lack of histopathology confirmation of mucosal inflammation (eosinophilic or neutrophilic) can bias the disease population entering a given study. Further confounding factors include the influence of coexisting diseases, pollution and cigarette smoke, and a need for same-site tissue comparisons, meticulous selection of relevant controls, and consensus on 'nondiseased' mucosal inflammatory cell populations and microbiology.Documentation of well defined patient and control groups, standardized specimen collection methods, and detection assays are critical in minimizing the bias and conflicting findings among investigators. With standardized sampling of tissue sites and tight controls on subcategories of CRS patients enrolled, studies will more likely identify the findings that can increase our understanding of the disparate group of CRS patients and identify new therapeutic targets in the CRS subcategories.