PURPOSE: Although many factors have been considered to predict the outcome after radical nephrectomy, renal cell carcinoma continues to behave unpredictably. In a retrospective study the correlation between microvascular tumor invasion and disease-free survival after surgery for renal cell carcinoma was analyzed. MATERIALS AND METHODS: Between 1980 and 1993, 180 patients (mean age 60 years) were followed for a mean of 52 months after radical or partial nephrectomy for clinically localized renal cell carcinoma. The relevance of microscopic vascular invasion was compared to classical tumor staging, grade and tumor diameter. RESULTS: Microscopic vascular invasion was found in 51 patients (28.3%), including 20 (39.2%) with progression (mean interval to progression 72 months). Of 129 patients with no pathological evidence of microscopic vascular invasion only 8 (6.2%) showed progression at a mean interval of more than 160 months. The difference in disease-free survival as a function of microvascular invasion was statistically highly significant (log rank p < 0.00001) and on multivariate analysis this parameter was by far the most relevant predictor of progression. CONCLUSIONS: In patients who underwent radical nephrectomy for clinically nonmetastatic renal cell carcinoma with microvascular invasion but without lymph node involvement or macroscopic vascular invasion the chance of disease progression is estimated at 45% within 1 year. Microvascular invasion is the single most relevant prognosticator after presumed curative radical nephrectomy for renal cell carcinoma.