Little is known about the clinical significance at the frequent association of 3p loss with 5q gain/loss in conventional renal cell carcinoma (RCC). We analyzed the clinical significance of copy number gain and loss at 5q21 approximately q23 combined with allelic loss of 3p25 (including the VHL gene). Fifty RCCs were examined by dual-color fluorescence in situ hybridization with DNA probes for D3Z1 (3cen), cCI3-865 (3p25.1 approximately p25.3), D5S23 (5p15.2), cCI5-243 (5q21.2 approximately q21.3), and cCI5-215 (5q22.3 approximately q23.2). In patients who had 3p loss, there was a significant association of loss at 5q22.3 approximately q23.2 with large tumors (>7 cm) and high-grade tumors (both P < 0.05), whereas gain at 5q22.3 approximately q23.2 was associated with low-grade tumors (P < 0.05). There was also a significant association loss at 5q21.2 approximately q21.3 high-grade tumors in patients with 3p loss (P < 0.05). Patients with 3p loss and gain at 5q22.3 approximately q23.2 had a significantly better disease-specific survival than those who had 3p loss without such gain (P < 0.05). Allelic loss of 3p25 including the VHL gene is thought to be an immediate event in the development of conventional RCC. Copy number gains or losses of 5q21 approximately q23 are thought to be events that lead to tumor progression although the clinical significance of either gains or losses is not well known.