An 82-year-old woman developed a well-differentiated squamous cell carcinoma that apparently arose in two discrete congenital cysts of the liver. Both cysts were lined predominantly by stratified squamous epithelium with extensive areas of dysplasia and foci of transition to in situ carcinoma and overt exophytic and infiltrating squamous cell carcinoma. A third intrahepatic cyst was lined entirely by bile duct-type epithelium and contained no tumor. The liver was massively infiltrated by the carcinoma, and there were metastases to the lymph nodes, lung, and bone marrow. Since a search for an alternative primary tumor site was unrevealing, the authors interpret this as a unique case of primary squamous cell carcinoma originating in congenital cysts of the liver.