The primary concerns of the surgical pathologist examining a biopsy specimen are whether a particular neoplasm is originating within the liver or is metastatic and, if a primary, whether differentiation is toward liver cells or bile ducts. The present study was undertaken in the hopes of providing a broader concept of the ultrastructural spectrum of liver cell carcinoma (LCC) and a more precise understanding of the changes occurring in these neoplasms with dedifferentiation. The 20 liver cell carcinomas, 13 bile duct carcinomas (BDC), and 3 hepatoblastomas were studied ultrastructurally and the findings correlated with light microscopic sections stained by hematoxylin-eosin and the periodic acid-Schiff procedure with and without prior diastase digestion. Immunocytochemical staining for alpha 1-antitrypsin was carried out on selected tumors. Ultrastructural study can be useful in the distinction of LCC from BDC in the minority of cases in which this is difficult by light microscopy. While true mixed tumors appear to be uncommon, duct formation can be simulated by LCC cells. The extent to which electron microscopy will enable the pathologist to separate metastatic neoplasms in the liver from primary liver cell tumors depends on the relative ultrastructural features. Assessment of the value of electron microscopy as an aid to light microscopy in the histologic grading of LCC and BDC will require further study.