Cyclooxygenase-2 (COX-2) displays anti-apoptotic functions related to angiogenesis or blocking of bcl-2 functions. COX-2 overexpression has been found in various human malignancies, including esophageal squamous cell carcinoma (ESCC). The present study examined correlations between expression of COX-2 mRNA and ESCC responses to chemoradiotherapy (CRT). Expression of COX-2 mRNA obtained from 29 biopsy specimens before CRT was quantified using reverse transcriptase-polymerase chain reaction (RT-PCR) using Sybr Green I on the Roche LightCycler system. CRT comprised 5-fluorouracil plus cisplatin and 40 Gy of radiation. Mean COX-2 mRNA score was significantly higher in tumors (1222) than in normal epithelium (50; p=0.05). Expression of COX-2 mRNA was high in 14 patients, low in 8 and absent in 7. The effective response to CRT was achieved in 18 patients. Mean COX-2 mRNA score was significantly higher in ineffective cases (2910) than in effective cases (190; p<0.05). CRT was more effective in patients with low COX-2 mRNA expression than in those with high expression. COX-2 mRNA expression in biopsy specimens was closely related to CRT effectiveness. Examination of COX-2 mRNA expression is useful for predicting the effect of CRT in patients with ESCC.