Tumor-associated tissue eosinophilia (TATE) has been related to prognosis in epithelial cancers, including cancers at several head and neck sites. This study prospectively examined 248 patients with stage III and IV laryngeal squamous cell carcinoma to determine prevalence and potential prognostic significance of TATE. Pretreatment tumor specimens were histopathologically evaluated. Presence and degree of TATE were analyzed with regard to other tumor characteristics, patient characteristics, and outcome criteria. Median follow-up was 48 months. Eosinophilia was found in 22.5% of specimens and was not related to tumor site, stage, patient age or sex, or treatment modality. Overall and disease-free survival rates and response to induction chemotherapy did not differ significantly with respect to TATE. This study represents the first long-term, prospective evaluation of TATE and its prognostic significance in a single head and neck site. Contrary to the findings of earlier preliminary reports, our results suggest that TATE is not a clinical useful prognostic parameter in advanced laryngeal squamous cell carcinoma.