Two cases of papillary cystic neoplasm (PCN) of the pancreas occurring in 18- and 34-year-old women are described. In both, the clinicopathologic features were typical. Immunohistochemical staining for neuron-specific enolase (NSE), S100 protein (S100), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and several peptide hormones was negative. Alpha-1-antitrypsin immunoreactivity was prominent, and its significance is discussed. Ultrastructural features were most compatible with partial acinar differentiation. Of the well-described cases of PCN, approximately 95% have occurred in women between the ages of 12 and 35, suggesting a role for hormonal factors in the pathogenesis of this tumor. Consequently, tumor tissue from one patient was assayed for estrogen and progesterone receptors: significant levels of high-affinity receptors were demonstrated for both hormones. Assays for the same receptors in five normal pancreases were negative. This constitutes the first reported measurement of these receptors in the PCN; the results indicate that the PCN may be another hormone-sensitive tumor.