Although heterotopia of pancreatic tissue is a developmental anomaly found in approximately 2% of all autopsies, pancreatic tissue within the thorax and mediastinum is uncommon. In most of these instances, the pancreatic acini and islets are components of gastroenteric duplication cysts, intralobar pulmonary sequestrations, or teratomas. We describe the clinicopathologic features and hormonal profile of a patient with an anterior mediastinal cyst formed entirely by pancreatic tissue. To our knowledge, the English literature reveals only two previous examples of this lesion. The patient, a previously healthy 16-year-old girl, was found to have a cystic lesion in the anterior mediastinum during investigation of an asymptomatic heart murmur. The lesion measured 12 cm in maximal diameter and contained dark, turbid fluid. The wall was fibrotic and contained a haphazard mixture of ducts, exocrine acini, and islets. In many areas, the ducts and islets formed ductuloinsular complexes resembling those seen in diffuse nesidioblastosis. Immunohistochemical examination showed that the islets contained an increased number of B and PP cells, recapitulating the hormonal profile of the ventral anlage of the fetal pancreas. The similarity between this lesion and a fetal pancreas was further supported by the presence of a significant number of islet cells containing gastrin. The histogenesis of this lesion is unclear; we think that this lesion represents a derivative of the ventral (anterior) primitive foregut, but unidirectional differentiation of a benign cystic teratoma cannot be excluded.