To determine the role of interphase cytogenetics as an adjunct in the cytodiagnosis of transitional cell carcinoma (TCC) in bladder washes, 40 separate samples were prospectively evaluated by conventional cytology, flow cytometry (FCM) and interphase cytogenetics using fluorescence in situ hybridization (FISH) to detect numerical chromosomal abnormalities involving chromosomes 8 and 12. The cases, all of which had subsequent histologic confirmation, were composed of 26 transitional cell carcinomas and 14 benign lesions. Cytology, FCM and FISH were concordant in 19 of 31 (61%) instances. The false-negative rates of the three parameters were as follows: cytology, 38.5%; FCM, 28.5%; FISH, 27%. The false-positive rates were 0%, 20% and 0%, respectively. The relatively lower sensitivity of cytology is attributed to sampling problems since 7 of the 10 false-negative cases were histologically high grade (grades 2 and 3) and should have been detected easily by conventional cytology if tumor cells were present. Thus, the sensitivity and specificity of FISH in detecting malignant cells of TCC in bladder washes is comparable to that of conventional cytology and FCM. When, as in the present study, there are insufficient numbers of cells for FCM analysis, the detection of numerical chromosomal abnormalities by FISH studies may serve as an adjunct in the diagnosis of TCC in bladder washes.