Patients with transitional-cell carcinoma (TCC) require careful follow-up due to the high risk of recurrence. Cystoscopy and biopsy are reliable but invasive, while urine cytology is plagued by low sensitivity. It has recently been shown that allelic abnormalities detected by microsatellite analysis of DNA extracted from urine can be used to diagnose TCC with high reliability. As this analysis by classic techniques is unfeasible in a clinical setting, we performed a pilot study to determine the possibility of applying quick DNA extraction methods with laser detection and computer-based analysis of 15 fluorescently labeled PCR amplified microsatellites to detect molecular anomalies in urine sediment in 25 TCC follow-up patients. Of the eighteen cases with recurrent TCC, 14 (78%) were positive by the molecular test whereas only eight (44%) were detected by cytology. Of the seven patients with negative cystoscopy, one resulted positive by the molecular test and had recurrent TCC six-months later. Thus, this microsatellite analysis correctly predicted the clinical diagnosis in 84% (21/25) of cases, compared to 60% by cytology. The application of these semi-automated procedures allows the analysis of 18 samples with 15 markers in one day, encouraging a more expedient introduction into routine clinical use.