AbstractBackgroundTumor necrosis factor–related associated‐inducing ligand (TRAIL) is a death ligand currently under clinical trials for laryngeal carcinoma.MethodsParaffin‐embedded tissues from 40 patients with laryngeal carcinoma and 20 patients with benign laryngeal pathologies were retrospectively analyzed using immunohistochemistry in terms of distribution and intensity, and for final analysis of immunoreactivity of receptors, H‐score was used. The study group was assessed in terms of localization, lymph node staging, tumor stage, overall survival, disease‐free survival, locoregional control, perineural invasion, and vascular invasion.ResultsThe H‐score of decoy‐R2 (DcR2) staining were increased significantly in tumor tissue (p = .04). A significantly greater increase in terms of H‐score of DR5 receptor staining (p = .06) was detected in tumor tissue.ConclusionTRAIL‐mediated gene therapy may not be effective. Indeed, the findings may indicate treatment resistance. TRAIL and TRAIL receptor levels were not associated with prognosis © 2015 Wiley Periodicals, Inc. Head Neck 38: E535–E541, 2016