PURPOSE: New, noninvasive methods are needed for the diagnosis, followup and screening of patients with bladder cancer. Three methods of detecting telomerase were evaluated in this aspect. MATERIALS AND METHODS: This study included 200 patients diagnosed with bladder carcinoma, 85 with benign bladder lesions and 30 healthy individuals who served as the control group. All underwent serological schistosomiasis antibody assay in serum, urine cytology and estimation of relative telomerase activity by telomeric repeat amplification protocol, human telomerase RNA by reverse transcriptase-polymerase chain reaction and human telomerase reverse transcriptase by real-time reverse transcriptase-polymerase chain reaction in urothelial cells from voided urine. RESULTS: The concordance between the positive rates of telomerase detected by the 3 methods was high (90% to 95%). Results were significantly higher in the malignant group than in the benign and control groups. There was a significant difference among the results of the 3 methods in relation to different clinicopathological factors. Overall the sensitivity of human telomerase reverse transcriptase for detecting bladder cancer was the highest compared to that of human telomerase RNA, relative telomerase activity and urine cytology (96%, 92%, 75% and 75%, respectively). Combinations of telomerase results with urine cytology were not useful except in cases of relative telomerase activity. CONCLUSIONS: Detection of human telomerase reverse transcriptase in urine by real-time polymerase chain reaction, followed by human telomerase RNA by reverse transcriptase-polymerase chain reaction, improves sensitivity and specificity for the diagnosis of bladder cancer. However, regarding cost-effectiveness, human telomerase RNA is superior.