INTRODUCTION: The limitations of serum PSA as a screening test to detect prostate cancer remain problematic, especially after an initial negative prostate biopsy. Detection of primary circulating prostate cells (CPCs) has been reported to be useful in the detection of prostate cancer in men with a serum PSA>4.0ng/ml. We present a prospective study comparing the detection of CPCs, total PSA, percent free PSA, digital rectal examination (DRE) and prostate volumen (PV) to establish a predictive model for the detection of prostate cancer in men with an indication for a second prostate biopsy. OBJECTIVE: To establish a predictive model for the detection of prostate cancer using the number of CPCs detected per sample, DRE, age, total serum PSA, percent free PSA and PV in men with an indication for a second prostate biopsy. METHODS AND PATIENTS: A prospective, observational study carried out in the Hospital de Carabineros de Chile, between 2006 and 2014 including 199 men undergoing a second prostate biopsy. The variables, number of CPCs detected (nCPC), DRE, age, PSA, percent free PSA and PV were registered for each patient and based on these findings and comparing them with the results of the prostate biopsy a multivariate logistic regression analysis incorporating forward predictors. The model was evaluated for co-lineal tendency, reliability and error specificity, and analyzed using non-parametric receiver operating characteristics and area under the curve decision for the combined model and for each variable separately. RESULTS: The single variable nCPC had a superior predictive value with an area under the curve of 0.89 (95% CI 0.83-0.94). The final model incorporated nCPC (OR: 2.03 95% CI 1.63-2.53) age (OR: 1.1 95% CI 1.04-1.17) and PV (OR: 0.96 95% CI 0.93-0.99) with an area under the curve for the combined model of 0.92 (95% CI 0.88-0.97). The combined model performed better than the variables used alone. CONCLUSIONS: The model incorporating nCPC, age and PV had a greater diagnostic yield for the predicting prostate cancer at second biopsy.