Pancreatic cancer is a lethal disease, with locally advanced pancreatic cancer (LAPC) having a dismal prognosis. For patients with LAPC, gemcitabine-based regimens, with or without radiation, have long been the standard of care. Irreversible electroporation (IRE), a non-thermal ablative technique, may potentially prolong the survival of patients with LAPC. In this article, the authors present a case of LAPC of the uncinate process (biopsy proven pancreatic neuroendocrine carcinoma) with duodenal invasion. The patient had a combination of chemotherapy and radiation therapy but was found to have stable disease. He then underwent intra-operative IRE with cholecystectomy, Roux-en-Y gastrojejunostomy and hepaticojejunostomy. He subsequently underwent percutaneous IRE 13 months post open IRE. The patient also completed peptide receptor radionuclide therapy and has been started on Lanreotide. Following combination therapy, the pancreatic tumor showed significant reduction in size, with patient survival at 53 months post-diagnosis at the time of writing.