Von Hippel-Lindau disease, a rare autosomal disorder, is associated with multiple lesions, including a high incidence of renal lesions and CNS hemangioblastomas. Renal lesions have traditionally been classified as either benign cysts or solid renal cell carcinomas with or without cystic degeneration. We examined seven kidney specimens from four patients with von Hippel-Lindau disease. We found that renal cysts form a histopathologic continuum ranging from benign cysts (with one to two cell layers of bland epithelium), atypical cysts (demonstrating epithelial hyperplasia with or without mild cytologic atypia), to malignant cysts harboring renal cell carcinoma. The presence of atypia or foci of carcinoma does not correlate with cyst size. Lesions that appear radiologically or grossly solid range from conventional solid renal cell carcinoma, sometimes evidencing cystic degeneration, to lesions that are predominantly hyalinized, fibrotic nodules. In contrast to simple cysts occurring in the general population, which are virtually always benign, renal cysts in patients with von Hippel-Lindau disease may contain occult carcinoma. Radiologic evaluation, visual inspection at surgery, and even frozen section analysis of cyst lesions cannot be relied on to detect small foci of carcinoma. The spectrum of pathologic changes and the multicentricity of the renal lesions in von Hippel-Lindau disease complicate the radiologic evaluation and surgical management of these patients.