Background Total prostate-specific antigen (tPSA) is the best available test for the detection of prostate cancer but it lacks specificity. The free-to-total ratio (F/T ratio) is used to increase specificity in the range of tPSA of 4–10 µg/L. Materials and methods Four hundred and seven biopsy results and quantitative tPSA and F/T ratio data were combined. Using the histological determination, normal/hyperplasia versus malignant as a gold standard, receiver operating characteristic (ROC) curves as well as the areas under the curve (AUC) for tPSA and F/T ratio were determined. The differences between the two AUCs were considered for various tPSA ranges and specificities of F/T ratio and tPSA were calculated. Results In the total group, there was a gain of specificity of 11% (from 23% to 34%) when the sensitivity was 92% (using a cut-off >0.28 for the F/T ratio and a cut-off >4 µg/L for tPSA). When considering the group of patients for which the F/T ratio is currently used (4–10 µg/L), the gain of specificity was 27% (from 2% to 29%). This implicates that the number of unnecessary biopsies taken will be reduced by 27%. Moreover, the AUC of the F/T ratio was significantly higher at an even broader range of tPSA, i.e. up to 40 µg/L. Conclusions This study demonstrates that the F/T ratio has better diagnostic performance than tPSA, not only in the grey zone of tPSA, but also outside the grey zone, i.e. up to 40 µg/L.