The prognosis of adenocarcinoma of the gastro-oesophageal junction is poor and only surgery yields long-term survival in no more than 30% of patients. We tested a new neoadjuvant chemo-radiotherapy regimen based on the administration of weekly docetaxel and cisplatin and continuous infusion of 5-FU with concurrent radiotherapy in order to evaluate its feasibility and efficacy. Thirty-three patients enrolled in a dose-finding study and observed at the 1st Division of General Surgery of the University of Verona between January 2000 and October 2003 underwent neoadjuvant chemo-radiotherapy for gastro-oesophageal junction adenocarcinoma (Siewert type I and II). The induction treatment was completed in 97.0% of cases with no treatment-related mortality. After completion of chemo-radiation 30 patients underwent surgery (90.9%) while three patients did not (progression in 2 cases and chemotherapy toxicity in one). Two operated patients did not undergo resection because of liver metastasis at laparotomy (respectability: 84.8%) and 3 more cases had incomplete tumour resection (R0-resectability: 75.8%). No postoperative in-hospital mortality was observed. A complete response (pT0N0) was achieved in 7 cases (23.3%) while minimal residual disease without evidence of lymph node involvement was found in a further 5 cases (16.7%). Worthy of note is the high rate of positive histopathological responses in the later period (6 out of 8) with 4 cases presenting complete responses. This protocol regimen proved to be feasible and well tolerated. Surgery-related deaths and morbidity were not increased. A high rate of positive pathological responses was obtained particularly in the later period of the study with the increased dosage of the protocol regimen.