There is increased deposition and lysis of fibrin in cancer, but little is known about the causes of this abnormal fibrin formation. This article reviews research on cancer procoagulant and presents some preliminary immunohistochemical studies. Cancer procoagulant was purified from a rabbit V2 carcinoma. It was a single polypeptide cysteine protease with a molecular weight of 68,000 daltons and an isoelectric point of 4.8-4.9. It initiates coagulation by directly activating factor X within the coagulation cascade. Its physical, chemical, and enzymatic properties distinguish it from serine proteases within the coagulation cascade and suggest that it is a protein from neoplastic cells. To determine whether cancer procoagulant was unique to the malignant state, procoagulant activity was assayed in extracts of normal and malignant tissue and serum-free medium from normal and transformed fibroblasts. Normal tissue and cells had procoagulant activity with characteristics similar to tissue factor, while malignant tissue and transformed cells had a procoagulant with the characteristics of cancer procoagulant, suggesting that cancer procoagulant is unique to the malignant state. An antibody to cancer procoagulant was used for horseradish peroxidase immunohistochemical staining fo cultured rabbit V2 carcinoma cells. These preliminary results support the concept that malignant cells produce the cancer procoagulant antigen.