OBJECTIVES: Complexed Prostate Specific Antigen (cPSA) testing offers an improved specificity compared to currently applied total PSA (tPSA) in the diagnosis of prostate cancer in patients at risk. Our objective was to assess the cost of cPSA if it would replace tPSA as first diagnostic test, based on medical management and cost data for Belgium. Both tests have the same unit cost. METHODS: A medical decision tree simulating a patient's flow and applying a time horizon of one year was developed in MS-Excel. Sensitivity and specificity data were obtained from published directly comparative clinical literature. An expert panel with 19 members (7 urologists and 12 general practioners) provided input data regarding the further diagnostic work-up in case of a positive PSA test and further therapeutical decisions and medical resource use in relation to the diagnostic outcomes (true and false positives and negatives). Costs of medical resources were obtained from the public health insurance perspective. RESULTS: When aiming for a target sensitivity of 90%, a diagnosis starting with cPSA costs €86.65 in total compared to €91.61 for tPSA. In a second analysis, if published manufacturer cut-off values were applied rather than a target sensitivity, total costs were €75.50 and €91.60 respectively. The savings were respectively €4.95 and €16.10 in favour of cPSA per patient. For a yearly cohort of 500,000 men, savings up to €8Mln could be realised. Sensitivity analyses on prevalence of prostate cancer and costs of diagnostic work-up showed that the results were robust (savings range €4.45-€5.46 in first analysis and €13.3-€18.8 in second). CONCLUSIONS: cPSA as standard screening test in prostate cancer in patients at risk appears to have a strong saving potential compared to the current use of tPSA. Further research should focus on the psychological impact of less false positive results.