Solid tumors require neovascularization for growth and metastasis. Vascular endothelial growth factor (VEGF) is a well-characterized inducer of angiogenesis, while, thrombospondin-1 (TSP-1) is thought to be an antiangiogenic factor. In this study, we examined the expressions of these antigens and their relationship with microvessel density, and determined their prognostic significance. One hundred specimens resected from patients with colorectal adenocarcinoma were examined using immunohistochemical methods. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumors that were VEGF-positive and TSP-1-negative than in other tumors. Patients with VEGF-positive tumors had a significantly worse prognosis than did those with VEGF-negative tumors, and TSP-1 expression was inversely correlated with prognosis. The frequency of hepatic recurrence was significantly higher in patients with tumors that were VEGF-positive and TSP-1-negative than in all other patients. In conclusion, VEGF and TSP-1 are important regulators of tumor angiogenesis, and combined analysis of VEGF and TSP-1 may be useful for predicting recurrence in patients with colorectal adenocarcinoma.