In a retrospective analysis at a single institution we evaluated the significance of various pathological phenomena on the disease-free survival of patients with radically resected renal cell carcinoma. Parameters considered were tumor extension (pT stage) according to the International Union Against Cancer, tumor invasion into the renal vein or vena cava (V stage), standard histological grading (G stage), nuclear grading (F stage) and microscopic venous infiltration. The pT stage had a significant impact on disease-free survival (p = 0.0004) of patients with radically resected tumors, as did G stage (p = 0.0001) and F stage (p = 0.002). In contrast to some previously reported results tumor extension to the renal vein and vena cava showed no influence on disease-free survival (p = 0.077). On the other hand, microscopic venous infiltration, defined as local tumor infiltration through all vessel structures including the endothelial layer leading to a free tumor extension into the vessel, had a significant impact on disease-free survival (p less than 0.0001). When stratifying either tumor size or nuclear differentiation against microscopic venous infiltration, the latter retained a superior influence on disease-free survival (p = 0.01 and p = 0.0079, respectively). We conclude that microscopic venous infiltration is the most important predictor of relapse in renal cell carcinoma.