This study aimed to establish clinically applicable cut-off values, propose a practical three-tier classification, and evaluate its diagnostic accuracy and clinicomolecular correlation with tumor aggressiveness.<h4>Methods</h4>FISH using VHL (3p25.3) and CEP3 probes was performed on 1748 RCC cases (1655 CCRCC, 48 papillary RCC, 45 chromophobe RCC). The gene discussed is CDC42EP3; the disease is nonpapillary renal cell carcinoma.