We assessed whether expression of excision repair cross-complementation group 1 (ERCC1) and/or thymidylate synthase (TS) can predict clinical outcome after preoperative chemoradiotherapy (CRT) in patients with localised oesophageal cancer. Paraffin-embedded pretreatment tumour specimens collected by endoscopic biopsy from patients treated with preoperative CRT (5-fluorouracil/cisplatin or capecitabine/cisplatin plus radiation) were analysed by immunohistochemical assay. Between March 1993 and June 2005, 129 patients were treated with preoperative CRT followed by surgery; of these, 108 biopsy specimens were available for analysis, and 40% and 35% were positive for ERCC1 and TS, respectively. Patients with ERCC1-negative (p<0.001) or TS-negative (p=0.04) tumours were significantly more likely to achieve pathologic major response. In multivariate analysis, ERCC1 was the only independent variable predicting pathologic response (p<0.001). Patients with ERCC1-negative tumours showed tendencies toward prolonged overall survival (p=0.10) and event free survival (p=0.08). Prospective studies are required to determine the benefit of preoperative CRT in ERCC1-negative tumours.