To analyze the clinical significance of copy number gain and loss at chromosome region 5q21 approximately q23, 105 nonpapillary renal cell carcinomas (RCC) were examined by interphase cytogenetic analysis using the dual-color fluorescence in situ hybridization (FISH) technique. DNA probes for D5S23 (5p15.2), cCI5-243 (5q21.2 approximately q21.3), and cCI5-215 (5q22.3 approximately q23.2) were used, and the signals for cCI5-243 and cCI5-215 were compared with those for D5S23 as the numerical control. Aneusomy (three or more copies) of chromosome 5 was found in 22 tumors (21.0%). Aneusomy was significantly correlated with loss at 5q21 approximately q23, while disomy with gain at 5q21 approximately q23 (P<0.05). Aneusomy was also significantly related to poor disease-specific survival (P<0.01). Gain and loss at cCI5-243 were seen in 34 (32.4%) and 59 (56.2%) tumors, respectively, while gain and loss at cCI5-215 occurred in 55 (52.4%) and 45 (42.9%) cases, respectively. The frequency of gain at cCI5-215 was significantly correlated with a smaller tumor diameter (7 cm or less, P<0.05), while loss with a larger one (>7 cm, P<0.05). Both loss at cCI5-215 and aneusomy of chromosome 5 were significantly related to poor disease-specific survival (P<0.05). In conclusion, alterations of chromosome 5 (including allelic loss of 5q22.3 approximately q23.2) could be a useful genetic marker for predicting the patient prognosis of RCC.