Previous studies have demonstrated von Hippel-Lindau (VHL) gene abnormalities in renal cell carcinoma. Archival cytologic samples of renal cell carcinomas (RCCs) from two patients were evaluated for allelic loss of the VHL gene. Small clusters of renal carcinoma cells were dissected from cytocentrifuge preparations under direct microscopic visualization followed by single-step DNA extraction and subsequent polymerase chain reaction (PCR). Amplification of DNA from the harvested tumor cells demonstrated a loss of heterozygosity at the VHL gene in five RCC specimens obtained from two patients. The combination of microdissection and PCR enabled DNA studies to be performed on a pure population of tumor cells isolated from heterogeneous samples containing admixed normal cellular elements. Selected genetic studies performed on microscopically targeted cells will help to further the biologic and cytomorphologic characterization of the targeted cell population.