<i>Introduction:</i> Tissue samples from prostate biopsy may contain atypical small acinar proliferation (ASAP): present guidelines recommend a repeat biopsy policy. This study attempted to identify clinical patterns that help predict cancer detection at second biopsy. <i>Materials and Methods:</i> From 1999 to 2005, 1,274 patients underwent a prostate biopsy: in 5.9% ASAP was found, and patients underwent a second biopsy. Uni- and multivariate analysis compared the clinical patterns of cancer patients with the no cancer group at second biopsy. <i>Results:</i> Univariate analysis showed significant differences in PSA ratio density, prostate volume, final PSA values and ΔPSA; at multivariate logistic regression analysis, only PSA ratio (OR = 0.743, 95% CI 0.620–0.891) and prostate volume (OR = 0.960, 95% CI 0.924–0.998) were predictive of malignancy. <i>Conclusions:</i> In our experience, PSA ratio and prostate volume seem to be independent predictors of prostate cancer at re-biopsy.