The aim of this study was to evaluate the potential diagnostic value of quantitative analysis of human telomerase reverse transcriptase (hTERT) mRNA in plasma for noninvasive diagnosis of prostate cancer (PCa). Expression levels of hTERT were analyzed by real-time quantitative RT-PCR in 68 patients showing elevated prostate-specific antigen (PSA) levels and a control group of 44 healthy volunteers. Sensitivity and specificity were determined and compared to the corresponding PSA values. Median values for hTERT gene expression in the PCa patients (0.72 ng; range 0.01-12.86) were statistically significantly higher (P < 0.001) than in the control group (0.13 ng; 0.02-0.35). Patients with clinically confirmed prostatitis showed lower plasma hTERT expression than PCa patients (0.29; 0.01-66.07). At a cutoff value of 0.35 sensitivity and specificity for the diagnosis of PCa were 81% and 60%, respectively. We suggest that hTERT mRNA in plasma is a very specific and sensitive method that may aid to differentiate between malignant and nonmalignant prostate tissue and may be a useful marker (in combination with PSA) for early PCa diagnosis.