We examined 12 patients with von Hippel-Lindau disease and renal cell carcinoma to characterize the pathological findings after renal surgery (total 161 lesions). Tissue from 15 partial nephrectomies and 1 radical nephrectomy was obtained for examination. Pathological evaluation identified 116 cystic lesions, 25 of which (21%) were malignant, and 45 solid lesions, 41 of which (91%) were renal cell carcinoma. Each kidney had a mean of 7.8 cystic and 3.0 solid lesions. Of 66 malignant lesions 35 (53%) were comprised of cells with only clear cell cytological features and 30 (45.5%) contained predominantly clear cells with scattered granular cells. One malignant lesion (1.5%) contained sarcomatoid renal cell carcinoma with clear and granular cells. Microscopic invasion of the pseudocapsule was common (13 of 25 clinically cystic tumors [52%] and 31 of 41 clinically solid lesions [76%]) but no tumor extended through the pseudocapsule. All lesions without a pseudocapsule were well circumscribed. Our study establishes the clear cell cytological features as the primary finding observed in patients with von Hippel-Lindau disease. Many cystic lesions contained renal cancer, demonstrating the need for removal of all cystic lesions when this can be safely performed. The well circumscribed nature of the tumors lends them to parenchymal sparing procedures.