Prominent eosinophilic infiltrates are an unusual finding in the pancreas. Eosinophilic pancreatitis is one rare etiology of pancreatic eosinophilia, but other described causes of eosinophilic infiltrates have also included pancreatic allograft rejection, pancreatic pseudocyst, lymphoplasmacytic sclerosing pancreatitis (LPSP), inflammatory myofibroblastic tumor, and histiocytosis X. In this study we describe the clinicopathologic features of three new cases of eosinophilic pancreatitis and conduct a retrospective 18-year institutional review of the myriad disease processes associated with pancreatic eosinophilia. In the files of the Johns Hopkins Hospital, <1% of all pancreatic specimens had been noted to show increased numbers of eosinophils. Eosinophilic pancreatitis itself was a rare etiology for pancreatic eosinophilia, with only one in-house case over the 18-year study period and two additional referral cases. Other disease processes associated with prominent eosinophilic infiltrates were more common and included pancreatic allograft rejection (14 cases), LPSP (5 of 24 total LPSP cases evaluated), inflammatory myofibroblastic tumor (4 cases), and systemic mastocytosis (1 case). Patients with eosinophilic pancreatitis showed two distinct histologic patterns: 1) a diffuse periductal, acinar, and septal eosinophilic infiltrate with eosinophilic phlebitis and arteritis; and 2) localized intense eosinophilic infiltrates associated with pseudocyst formation. All three patients with eosinophilic pancreatitis had peripheral eosinophilia, and all had multiorgan involvement. One patient with LPSP also had marked peripheral eosinophilia, and 5 of 24 LPSP cases demonstrated prominent eosinophilic infiltrates in the gallbladder, biliary tree, and/or duodenum. Notably, not all of these patients with LPSP with prominent eosinophils in other organs had increased eosinophils in the pancreas itself. These results emphasize the infrequent nature of pancreatic eosinophilia and its multiple potential disease associations. True eosinophilic pancreatitis, although a fascinating clinicopathologic entity, is one of the rarest causes of pancreatic eosinophilia.