Human fascin is a highly conserved 55-kD actin-bundling protein which shares extensive sequence homology with sea urchin fascin and the Drosophila singed gene (sn) protein. Fascin, encoded by the human homolog for sn (hsn) gene, has been localized to microspikes and stress fibers of cultured cells where it is thought to be involved in the formation of microfilament bundles. Fascin has been localized by immunohistochemistry to the cytoplasm of a number of cell types. Fascin has been found to be strongly expressed in interdigitating reticulum cells (IDC) from the T-cell zones of the lymph node. Dendritic cells of the subcapsular area and of the reticular network also stain positively. Follicular dendritic cells (FDC) of the lymph node and spindle cells (interstitial dendritic cells) in perinodal tissue have been shown to exhibit variable immunostaining. Strong immunoreactivity has been observed in dendritic cells of the thymus, spleen and peripheral blood (veiled cells). Fascin has also been demonstrated in the cytoplasm of histiocytes, smooth muscle cells, endothelial cells, squamous mucosal cells and lining cells of splenic sinuses. Fascin expression has been demonstrated in the cytoplasm of Reed-Sternberg cells and their variants. Anti-fascin was found to immunostain most Reed Sternberg cells and their variants in the majority of cases of Hodgkins lymphoma evaluated, including nodular sclerosis, mixed cellularity, lymphocyte depletion and unclassified types of Hodgkins disease. Among non-Hodgkins lymphomas and other lymphoid neoplasms, only a minority of cases were immunoreactive. A decrease of fascin immunoreactivity in HLP was found to be associated with advanced disease and destruction of the dendritic network. Fascin immunostaining has also been demonstrated in a subset of mainly high grade breast carcinomas. Expression of fascin was found to correlate with tumor grade, Ki-67 proliferation index and p53 overexpression and to be inversely related to estrogen receptor expression.