Nitric oxide (NO) plays important biological roles in cardiovascular, nervous and immune systems, and is synthesized by nitric oxide synthase (NOS). Intracellular NO is known to cause DNA damage as a mutagen. We examined the expression of cytokine-inducible NOS (iNOS) in human esophageal squamous cell carcinomas. Weak iNOS immunoreactivity was seen in the basal and parabasal layers of non-neoplastic esophageal stratified squamous epithelium. iNOS expression was detected in 50 (87.7%) of the 57 esophageal squamous cell carcinomas, regardless of the depth of tumor invasion, histological differentiation and lymph node status. Early-stage cancers, i.e. mucosal squamous cell carcinomas, also showed significant iNOS expression. We speculate that increased iNOS expression is associated with the carcinogenesis of human esophageal cancer.