A 53-year-old man was found to have a giant 16 × 6-cm hemorrhagic and cystic mass centered on the pancreas and duodenum. Initially diagnosed as a pancreatic pseudocyst at the time of autopsy, the cystic mass was later determined by histologic examination to be a true diverticulum of the duodenum as microscopic examination of the wall revealed 2 layers of muscle, as well as a neutrophilic infiltrate. While the cause of death of the individual was certified as methamphetamine toxicity, cardiomegaly and probable dehydration associated with a giant duodenal diverticulum were listed as contributory conditions. While duodenal diverticula in general are relatively uncommon findings, an extramural, true, giant duodenal diverticulum that is inflamed is a rare clinical or autopsy finding, with only 2 case reports identified in the clinical medical literature and none in the forensic literature.