Pancreatic cancer has a very poor prognosis resulting in the death of 98% of patients. Pain may be severe and difficult to treat. Management of pain includes chemotherapy, radiotherapy, pharmacologic treatment, and neurolytic celiac plexus block. Recent reviews of the efficacy of neurolytic celiac plexus block however, have reached conflicting conclusions. In this paper, we present two patients with severe pancreatic cancer pain resistant to pharmacologic treatment. Analgesic effect following repeated neurolytic celiac plexus blocks with alcohol was limited in time. Post‐mortem neurohistopathologic examination of the celiac plexus revealed an abnormal celiac architecture with a combination of abnormal neurons with vacuolization and normal looking neuronal structures (ganglionic structures and nerve fibers) embedded in fibrotic hyalinized tissue. Our results show that a neurolytic celiac plexus block with alcohol is capable of partially destroying the celiac plexus. These findings may explain the significant but short‐lasting analgesic effect following neurolytic celiac plexus block with alcohol.