Radiofrequency ablation of the pancreas represents a more effective tumor-destruction method compared to other ablation techniques. The endoscopic ultrasound guided radiofrequency ablation is indicated for locally advanced, non-metastatic pancreatic adenocarcinoma, without the need of general anesthesia and fast recovery. The main limitations are the encasement of the mesenteric vessels or of the common bile duct in the head pancreatic tumours. The technique is feasible, effective and relatively safe in porcine models, with minimal evidence of fat necrosis in intra-pancreatic and/or extra-pancreatic adipose tissue. It has been successfully applied on insulinomas and pancreatic adenocarcinoma in humans, with few complications, such as duodenal bleeding or mild abdominal pain. Other side effects as biliary fistula, pancreatic fistula or acute pancreatitis seen in intraoperative settings of radiofrequency ablation, have not been reported in endoscopic ultrasound guided radiofrequency ablation.