BACKGROUND: This study was designed to evaluate the feasibility of a neo-adjuvant combined chemo-radiotherapy in patients with localized squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: Forty-two patients with squamous cell carcinoma of the esophagus, stages II and III (or stage I if considered to be poor candidates for immediate curative surgery), age less than 70 years and WHO performance status 0 to 2, were enrolled in a study of radiotherapy combined with chemotherapy, consisting of 2 (operated patients) or 3 (nonoperated patients) courses of cisplatin, vindesine, mitomycin-C or cisplatin, vinblastine. Surgery was routinely proposed to patients. RESULTS: Thirty-seven patients (88%) received full preoperative therapy. Of 30 patients responding to this preoperative therapy, 12 had a third cycle of treatment and 15 had esophagectomy. Three of the operated patients had no pathological evidence of residual tumour. Median survival of all 42 patients is 11 months and the 2-year survival rate is 29%. There is no difference in survival among responding operated or non-operated patients. Our group represents 95% of all eligible cases of squamous cell carcinoma of the esophagus occurring in Geneva during the study period. CONCLUSION: Our series gives a realistic view of the median survival of a population of patients eligible for neo-adjuvant therapy of esophagus cancer, and suggests that secondary surgery might not improve the patient survival. Furthermore, non-selected patients are at high risk for therapy-related death.