The identification of Kupffer cells highlighted by positive immunostaining for vimentin on direct smears was found to play an important role in the differentiation between primary and metastatic liver carcinoma, by fine needle aspiration biopsy. The Kupffer cell, identified by vimentin staining, is spider-or star-shaped with multiple elongated and slender cytoplasmic processes. Direct smears obtained by fine needle aspiration cytology from 24 cases of hepatocellular carcinoma, 4 cases of cholangiocarcinoma, and 17 cases of metastatic carcinoma were stained with vimentin. The cytologic diagnoses were verified by histologic and/or clinical follow-up. All 24 cases of hepatocellular carcinoma, contained significant number of vimentin-positive spider cells within tumor clusters. There were at least three spider cells present within each tumor cluster, involving at least 50% of the tumor clusters. The spider cells were not only found in the well-differentiated type but also in the moderately and poorly differentiated types of the hepatocellular carcinoma. However, the tumor cells from 4 cholangiocarcinoma cases and 17 metastatic carcinomas contained no or few spider cells in the tumor clusters. The presence of numerous vimentin-positive spider-shaped Kupffer cells within tumor clusters constitutes strong evidence in favor of a diagnosis of hepatocellular carcinoma.