Biliary cystadenomas with mesenchymal stroma are neoplasms whose growth may be hormone sensitive. This study profiled the immunohistochemistry of these lesions to clarify the pathophysiology and define clinical management. Twelve patients with biliary cystadenomas were identified. Tissue was tested with a panel of probes including estrogen and progesterone receptors and compared to pancreatic and ovarian cystadenomas. Epithelial ER, PR, CD117, or SMA expression was negative in all three tumors. Epithelial CD10 expression was seen in 60% biliary, 75% pancreatic, and 0% ovarian tumors. Biliary cystadenoma stromal expression was ER+ (70%), PR+ (60%), CD10+ (40%), and c-kit+ (0%). Symptoms were seen in 92% patients. Percutaneous sclerotherapy and incomplete resection were associated with recurrence. Enucleation was the least morbid surgical technique. A role for hormonally mediated growth of biliary cystadenomas occurring through the stroma, rather than the epithelium, is suggested. Management remains complete surgical resection.