INTRODUCTION: Bladder cancer diagnosis and surveillance is costly and frequent. Urinary cytology is used with cystoscopy in the diagnosis and surveillance of bladder cancer with little evidence to support this practice. Nuclear Matrix Protein-22 (NMP-22) is a marker of urothelial cell death and is elevated in the urine of patients with bladder cancer. Our study compares the performance of NMP-22, urinary cytology and office cystoscopy when utilized in a Veteran Affairs urology practice for 1 year. MATERIALS AND METHODS: A total of 391 consecutive office cystoscopy procedures performed over 1 year were included in the study. NMP-22 and cytology were performed on the urine specimens of patients presenting for cystoscopy. Tumor resection/bladder biopsy was performed when cystoscopy, NMP-22 or urinary cytology were abnormal. RESULTS: Cystoscopy, NMP-22, and urinary cytology data were available in 351 encounters and 69 tumor resections were performed. Urothelial carcinoma bladder (UCB) was identified in 37 bladder specimens. NMP-22, urinary cytology and cystoscopy demonstrated sensitivity and specificity of (51%/96%), (35%/97%), and (92%/88%), respectively. NMP-22 cost $8,750 in the study group and urinary cytology cost $52,500 in the same group. CONCLUSIONS: This study demonstrates cystoscopy was the most sensitive test in the diagnosis of UCB. NMP-22 had a higher sensitivity than urinary cytology and similar specificity to cytology. Additional urinary marker testing has a limited role in the management of bladder cancer in the office setting. When adjunct testing is desired in the diagnosis and surveillance of bladder cancer, NMP-22 is a cost effective alternative to urinary cytology.