We compared immunohistochemical expression of hepatocyte growth factor (HGF), c-met, alpha-inhibin, estrogen receptor (ER), and progesterone receptor (PR) in 10 pancreatic mucinous cystic neoplasms (PMCNs), 8 hepatobiliary cystadenomas (HBCs), and 6 simple liver cysts (SLCs).All HBCs and PMCNs were in women (mean ages, 45.7 and 54.9 years, respectively; P > .05). All HBCs had abundant stroma; PMCN stromal density was more variable (score, 3.0 vs 1.8; P < .05). Stroma in HBCs had greater ER and PR staining (both P < .05) and more consistent, focal, strong reactivity for alpha-inhibin than PMCNs (P < .05). SLCs were found in men and women, lacked ovarian-type stroma, and were negative for ER, PR, and alpha-inhibin. HGF expression was not significantly different in the epithelium of HBCs, PMCNs, and SLCs; c-met expression in the epithelium of HBCs and PMCNs was significantly stronger than in SLCs (P < .05). Differences in stromal density and ER, PR, and alpha-inhibin immunoreactivity in HBCs and PMCNs suggest that different hormonal environments in the liver and pancreas contribute to stromal variation. Up-regulation of c-met in HBCs and PMCNs suggests c-met activation in the pathogenesis of pancreaticobiliary cystic neoplasms.