Background To evaluate the correlation between the side of positive biopsy (Bx) and the risk of lymph-node metastases (LNMs) on each side and to quantify the risk of contralateral LNMs in patients with unilateral positive biopsy. Methods We analyzed the outcomes of 1599 patients with complete data regarding the sides of positive Bx and LN (lymph-node). By dividing each prostate into two separate sides, we assessed the accuracy of the side-specific Bx details in determining the side of positive nodes; the area under the receiver-operating characteristic (ROC) (AUCs) was used. For patients with unilateral positive Bx, we assessed the risk of homolateral and contralateral LNMs according to the number of total Bx taken and the preoperative risk of LN invasion. Results Considering the 3198 prostate sides, there was a strict correlation between the side of positive Bx and the side of LNMs. The ratio of positive/total Bx was more informative than the number of positive core. The AUC for ipsilateral LNMs was significantly higher than that for contralateral LNMs (P = 0.039). In the 805 patients with unilateral positive Bx, the percentage of contralateral LNMs was >30% even considering a more meticulous biopsy scheme and increased in the patients at a higher clinical risk for LN invasion. Conclusion PCa preferentially metastasizes to ipsilateral LNs but >30% of contralateral LNMs are present. A unilateral LN dissection that is limited to the tumor-bearing side of the gland should not be recommended because of the substantial risk of missing contralateral metastases. © 2013 Elsevier Ltd. All rights reserved.