OBJECTIVE To assess the clinical performance of ImmunoCyt in the detection of upper urinary tract transitional cell carcinoma (UT-TCC). This newly developed immunocytochemical test detects three cellular markers specific for TCC. METHODS Thirty-seven patients with symptoms and/or findings on imaging suggestive of UT tumors were prospectively evaluated. All patients underwent a standard cytologic evaluation and ImmunoCyt testing of voided urine, as well as imaging studies. Urine samples were also obtained from the UT of 32 patients by ureteral catheterization and tested by cytologic analysis and ImmunoCyt. RESULTS Sixteen patients had UT-TCC as documented by the final histologic evaluation. The sensitivity of testing the voided urine from 37 patients was 50% for cytologic analysis, 75% for ImmunoCyt, and 87% for both methods combined. The cytologic evaluation detected no G1, 1 (17%) of 6 G2, and 7 (100%) of 7 G3 tumors. ImmunoCyt detected 1 (33%) of 3 G1, 6 (100%) of 6 G2, and 5 (71%) of 7 G3 tumors. The sensitivity in the 32 urine samples obtained from the UT was 82% for cytologic analysis, 91% for ImmunoCyt, and 100% for both methods combined. Cytologic analysis detected all G2 and G3 (100% sensitivity) and no G1 tumors. ImmunoCyt detected 2 (100% sensitivity) of 2 G1, 4 (100%) of 4 G2, and 4 (80%) of 5 G3 tumors. The test specificity, calculated in 21 patients free of TCC, was 100% for cytologic analysis in voided and ureteral urine specimens and 95% and 100% for ImmunoCyt in voided and ureteral urine samples, respectively. CONCLUSIONS The results of this preliminary study show that ImmunoCyt complements cytologic analysis in detecting UT-TCC, mainly because of its high sensitivity to low-grade TCC. The combination of cytologic testing and ImmunoCyt gives 100% sensitivity in detecting UT-TCC in UT urine samples.