RXRalpha is an obligatory heterodimerization partner in many signal transducing pathways. To evaluate RXRalpha expression during laryngeal carcinogenesis, immunohistochemistry was performed on laryngeal epithelial specimens of 154 patients with normal-appearing, hyperplastic, dysplastic laryngeal epithelium and squamous cell carcinoma. RXRalpha up-regulation was detected from the early stages of laryngeal carcinogenesis compared with normal epithelium. Statistical analysis and correlation of the intensity of nuclear immunostaining among the various histologic entities revealed statistically significant results. We pose that RXRalpha overexpression might represent an early protective effect in the process of laryngeal carcinogenesis that might be overwhelmed by an epigenetic disability in forming heterodimers with PPARgamma.