BACKGROUND: Tumor growth and metastasis depend on angiogenesis. Angiogenesis correlates with the expression of vascular endothelial growth factor (VEGF) and with the prognosis in some cancers. Angiogenesis may also play an important role in the growth and the metastasis of thyroid cancer. We determine whether the expression of VEGF and its receptors (flk-1/KDR, flt-1) correlates with vascularity, invasion to adjacent structure and lymph node metastasis of thyroid cancers. METHODS: Sixty-five specimens obtained from patients with benign thyroid disease and thyroid cancers investigated by immunohistochemical staining for factor VIII, VEGF, flk-1/KDR and flt-1. Vessels were counted by light microscopy (x200), and the intensity of staining for VEGF and receptors was assessed on a scale of 1 to 4 . Correlations between the expression of VEGF, microvessel density and various clinicopathologic factors were analyzed. RESULTS: 1) There were no differences in microvessel counts and expressions of VEGF and its receptors among sex, age and tumor size. 2) Microvessel counts in thyroid cancers (mean SD: 91.1+/-30.4, x200), especially anaplastic cancers (159.0+/-14.1) were higher than in follicular adenomas (56.3 13.6). 3) The expressions of VEGF, flk-1/KDR and flt-1 were higher in thyroid cancers (2.7+/-1.0, 2.1+/-0.9, 2.2+/-0.9) than in follicular adenomas (1.4+/-0.5, 1.4+/-0.5, 1.4+/-0.5), the expressions of VEGF, flk-1/KDR and flt-1 in anaplastic cancers (3.8+/-0.5, 3.8+/-0.5, 3.5+/-0.6) were higher than in differentiated cancers (papillary and follicular). But there were no differences of microvessel density and the intensity of VEGF, flk-1/KDR and flt-1 expression between absence and presence of the invasion to adjacent structure and lymph node metastasis in cancers. 4) The intensity of VEGF expression correlated with microvessel densities and that of its receptors. CONCLUSION: Angiogenesis and VEGF expression in thyroid cancer correlated with the grade of differentiation. But we did not found any differences in angiogenesis and VEGF expression with or without invasion to adjacent structures and lymph node metastasis in differentiated thyroid cancer. In the future, further study, including recurrent and distant metastatic thyroid cancers, will be needed.