The aim of this study is to evaluate the relationship between tumor angiogenesis and microvascular invasion, and the subsequent development of metastatic disease in patients undergoing surgery for renal cell carcinoma (RCC). The study group consisted of 102 patients who underwent surgery for RCC between the years 1990 and 1997 in our institute with a mean follow up period of 81.3 months. Paraffin blocks were stained for Factor VIII - related antigen and CD34 which decorate endothelial cells in order to assess angiogenesis and microvascular invasion and their relevance for developing metastatic disease. When Factor VIII- related antigen staining was used we found that the microvessel count correlated with the development of metastatic disease with a mean count of 49.7 for patients with no evidence of disease and a mean count of 95.5 for patients who developed metastatic disease (p<0.05). We also found that microvascular invasion correlated with the development of metastatic disease. It was demonstrated in 55.5% of patients who developed metastatic disease versus 23.8% of patients with no evidence of disease with Factor VIII staining (p<0.05), and in 33.3% and 7.1%, respectively (p<0.05) with CD34 staining. This study suggest that demonstration of intense angiogenesis and micro-vascular invasion may be a predictor of a more aggressive tumor mandating closer follow up and consideration of adjuvant therapy.