Multimodal therapy comprising neoadjuvant chemotherapy and radiation therapy prior to radical resection is increasingly utilized in gastroesophageal cancer. The achievement of a complete pathological response (pCR) or a major response is associated with an improved survival. However, up to 70% of patients show an incomplete or no response to the neoadjuvant regimen, and the identification of factors which predict a response would be of considerable clinical benefit. A retrospective analysis of a prospectively updated esophageal cancer database was performed. The predictive values of the following clinicopathological factors were investigated: age, sex, tobacco, alcohol, weight, clinical history, tumor type, site, length, width, morphology and differentiation. Statistical analysis was performed using Chi-square test with Pearson's test or Kruskal–Wallis test. One hundred and seventy-six patients were identified who had undergone neo-adjuvant chemoradiotherapy at St James's Hospital Dublin, between January 1990 and June 2003. A complete pathological response was seen in 40 cases (23%). There was a significant (P < 0.05) relationship between response to chemoradiotherapy and pretreatment tumor length. The median tumor length in the pCR group was 2 cm (1–5 cm) compared with 3 cm (2–7 cm) in non-responders (P < 0.05). Body weight, sex, tobacco or alcohol usage, tumor site, or differentiation were not predictive of response, although a trend (P = 0.08) was observed for squamous cell cancer compared with adenocarcinoma. Smaller tumor length was predictive of a greater response to chemotherapy and radiation therapy. This may reflect different tumor biology, perhaps with acquired resistance to treatment-induced apoptosis in the larger tumors. A simpler explanation is that the existing dose and treatment schedule for combination chemoradiotherapy is suboptimal in patients with larger tumors.