BACKGROUND Thrombospondin in a 450-kilodalton glycoprotein, first described as a secretion product of thrombin-stimulated platelets. In a recent study, thrombospondin was discovered not only to accelerate platelet aggregation and to promote construction of the extracellular matrix but also to be involved in the progression of malignant tumors. In another study, plasma thrombospondin was reported to be elevated in patients with colorectal carcinoma with hepatic metastasis. Moreover, venous invasion in colorectal carcinoma is well known to be involved profoundly in organ metastasis. METHODS Blood samples from patients with colorectal carcinoma were collected preoperatively by venipuncture using ice-chilled tubes, and immediately centrifuged at 4 degrees C. The plasma was aspirated and frozen until the concentration of thrombospondin was measured using a competitive enzyme-linked immunoadsorbent assay. The degree of venous invasion in each case was evaluated pathologically using resected specimens to examine for any correlation with the plasma thrombospondin level. RESULTS The plasma thrombospondin level was significantly higher in those patients with malignant venous invasion than in those patients with no venous invasion, according to Dukes staging. There was a direct correlation between the plasma thrombospondin level and the degree of venous invasion. CONCLUSIONS Venous invasion by colorectal carcinoma was found to play an important role in the elevation of the plasma thrombospondin level. Alternatively, a high concentration of thrombospondin may support metastasis and progression of this malignancy.