A series of studies carried out by the Gastrointestinal Tumor Study Group have shown the efficacy of the combination of external beam radiotherapy (ERT) and 5-fluorouracil (5-FU) chemotherapy (CHEM) in unresectable and resectable tumors of the exocrine pancreas. In the former in particular, this method was shown to be superior to ERT alone as well as to polychemotherapy alone. In these studies 5-FU was administered during (concomitant chemotherapy: C-CHEM) or after ERT (adjuvant chemotherapy: A-CHEM). This led several authors to consider this combined treatment as reference standard for pancreatic carcinoma. Its prognosis is still definitely poor because of the difficult local eradication as well as because of the frequent early distant spread, especially at the abdominal level (hepatic and peritoneal). An improvement of present results may stem from the combination of ERT+C-CHEM +/- A-CHEM with methods of dose intensification at the local level (e.g. IORT) concurrently with the use of treatments aiming at a better control of the abdominal spread (e.g. ERT+C-CHEM for prophylaxis of the liver or upper abdomen).