Lack of investment for magnetic resonance (MR) fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway. We developed a coordinate-based method to support cognitive targeted prostate biopsies and then performed an audit on cancer detection and the location of lesions. In each patient, the prostate is considered as two separate hemiprostates, and each hemiprostate is divided into 4 × 4 × 4 units. Each unit is therefore defined by a three-dimensional coordinate. We prospectively applied our coordinates approach to target 106 prostatic lesions in 93 men. Among 45 (of 106; 42.5%) lesions positive for cancer, 27 lesions (60.0%) harbored clinically significant disease. PSA density was significantly higher in patients with proven cancer (median: 0.264 ng ml −2 ) when compared to the noncancer group (median: 0.145 ng ml −2 ; P = 0.003, Wilcoxon rank-sum test). Lesions with Prostate Imaging-Reporting and Data System (PIRADS) score of 5 were found to have a cancer incidence of 65.2%, while PIRADS 4 and 3 lesions have a lower risk of cancer detection, as expected, at 37.3% and 31.3%, respectively. The probability of a lesion being cancerous in our series significantly decreases as we go from the “apex-to-base” dimension (odds ratio [OR]: 2.62, 95% confidence interval [CI]: 1.55–4.44, P = 0.00034). Our analysis also indicates that the probability of cancer decreases as the prostate volume increases (OR: 1.03, 95% CI: 1.01–1.05, P = 0.00327). Based on this feasibility study, the use of coordinates to guide cognitive targeted prostate biopsies warrants future validation study in additional centers.