Double-target in situ hybridization technique (ISH) was applied to 37 cases of bladder cancer to detect numerical aberrations of chromosomes 7, 9, 10, and 11 by centromeric DNA probes. Of 33 evaluable cases, 29 (88%) demonstrated chromosome aberrations. In 17 cases with diploid pattern as measured by flow-cytometric DNA analysis (FCM), 15 (88%) demonstrated chromosome aberrations. Of these, trisomy 7, monosomy 9, and trisomy 10 were detected in three, three, and one case, respectively, as a single chromosome aberration. In 14 (88%) of 16 cases with an aneuploid DNA pattern, chromosome aberrations for two or more chromosomes were demonstrated. A significant correlation was observed between grade of chromosome aberrations and tumor grade (p < 0.01, Fisher's test), between number of spots for chromosome 7 and peak value in FCM (p = 0.015, by Spearman rank order test). In eight cases, chromosome aberrations in the tumor were compared with the corresponding pattern in the grossly normal and histologically benign mucosa. Trisomy 10 and monosomy 9 were detected as chromosome numerical aberrations in the histologically normal mucosa, consistent with aberrations in the corresponding patients. We conclude that trisomy 7, monosomy 9, and trisomy 10 may be early events in the evolution of bladder cancer.