Cyclooxygenase (COX) is a key enzyme in arachidonic acid metabolism. Two isoforms of this enzyme have been identified: constitutive COX-1 and inducible COX-2. Recently, expression of COX-2 has been found in several human carcinomas. COX-2 expression may contribute to the synthesis of prostanoids, which relate to carcinogenesis and tumor progression. We investigated the expression of COX-2 in 175 human esophageal squamous cell carcinoma tissues using immunohistochemistry and evaluated the relationship with clinicopathological findings. In addition, due to the known relevance of p53 to carcinogesis, we evaluated the expression of COX-2 and p53. Interestingly, cancer tissues with high COX-2 expression were found significantly more often in the middle and lower esophagus than in the cervical and upper esophagus (p = 0.0014). No significant differences were observed in other clinicopathological data such as age, sex, histopathological grading, lymphatic invasion, venous invasion, TNM clinical classification and patient prognosis. p53 expression was associated with the expression of COX-2 (p = 0.0122). Our findings suggest that COX-2 may play a role in the development of squamous cell carcinoma in the lower part of the thoracic esophagus.