Urothelial carcinoma (UC) is the 5th most common cancer in the United States. Early detection would improve the outcome of these patients. Currently, urine cytology or cystoscopy are used for early detection of UC. Urine fluorescence in situ hybridization (FISH) analysis is a novel noninvasive molecular test to detect genetic abnormalities in urine samples. We evaluated the efficacy of the noninvasive urine FISH test in improving the quality of care of UC patients. We retrospectively analyzed urine FISH tests performed in our institution from 01/2005 to 06/2012. Patients were followed up to determine any positive cytology or biopsy. Data were statistically analyzed. Of 305 cases, 49 cases (16.1%) were positive including 14 for screening (initial diagnosis of UC) and 35 for surveillance of UC (to monitor disease recurrence). Of the 14 screening cases, 7 were confirmed on subsequent biopsy as high grade UC; 2 had prostate adenocarcinomas, and in 5, urine cytology was negative and no biopsy was done. Of the 35 surveillance cases, 33 cases were biopsy-confirmed UC: 21 high-grade and 12 low-grade; 1 case had a positive cytology but no biopsy was done and 1 had no cytology or biopsy. Our findings indicate that urine FISH test can detect genetic abnormalities indicative of malignancy in 16% cases. It is clinically useful in detecting index cases to screen for UC and surveillance of UC cases on treatment to monitor disease recurrence at times earlier than biopsy. This is because genotypic expression precedes phenotypic expression of the malignancy. Thus in the correct clinical context, when done in conjunction with urine cytology and biopsy, the urine FISH test is helpful in improving early detection of new cases and surveillance of patients on therapy, ultimately improving the quality of care of UC patients.