Background. Multivariate models are used to increase prostate cancer (PCa) detection rate and to reduce unnecessary biopsies. An external validation of the artificial neural network (ANN) “ProstataClass” (ANN-Charité) was performed with daily routine data. Materials and Methods. The individual ANN predictions were generated with the use of the ANN application for PSA and free PSA assays, which rely on age, tPSA, %fPSA, prostate volume, and DRE (ANN-Charité). Diagnostic validity of tPSA, %fPSA, and the ANN was evaluated by ROC curve analysis and comparisons of observed versus predicted probabilities. Results. Overall, 101 (35.8%) PCa were detected. The areas under the ROC curve (AUCs) were 0.501 for tPSA, 0.669 for %fPSA, 0.694 for ANN-Charité, 0.713 for nomogram I, and 0.742 for nomogram II, showing a significant advantage for nomogram II (P = 0.009) compared with %fPSA while the other model did not differ from %fPSA (P = 0.15 and P = 0.41). All models overestimated the predicted PCa probability. Conclusions. Beside ROC analysis, calibration is an important tool to determine the true value of using a model in clinical practice. The worth of multivariate models is limited when external validations were performed without knowledge of the circumstances of the model's development.