Patients with cancer experience a much higher than expected incidence of thromboembolic disorders, commonly referred as Trousseau syndrome. Although this association has been well documented, the etiology of the hypercoagulable state is not known. The expression on tumor cells of tissue factor (TF), a membrane-bound lipoprotein that functions as a cofactor to factor VIIa in the initiation of the extrinsic pathway of blood coagulation, has been postulated as a possible mechanism. Whereas the distribution of TF in normal tissues is known, no large survey of TF expression in malignant tissues has been reported. In this study a polyclonal, monospecific rabbit anti-human TF IgG was used for immunohistochemical localization of TF antigen in 85 different tumor specimens. In general, cell types which normally express TF continued to do so after malignant transformation (41 of 60 epithelial tumor specimens were positive for TF). Tumors of nonepithelial origin frequently lacked TF, with only 3 of 19 specimens containing evidence of TF antigen. In addition five of six benign tumors did not express TF. Many tumor types commonly associated with Trousseau syndrome, for example lung, pancreatic, breast, colon and gastric carcinomas, stained positively for TF. Based on this survey, it appears that TF expression by tumors may be an important factor in the pathogenesis of a hypercoagulable state in some patients with cancer.