The wide adoption of MRI and MRI-directed biopsies in the diagnostic workup of suspected prostate cancer (PCa) has ignited discussions about the appropriate balance between the benefits and harms of the biopsy decisions. The benefits arise from true MRI results and harms arise from false results. The very high sensitivity and negative predictive value of MRI (about 90% on average for both), and a low false-negative rate enable many men in “screening” cohorts to avoid biopsies. Although the specificity (about 70%) and positive predictive values are more variable, it has been found that there is a possible benefit of reducing the number of cores for men undergoing a biopsy, because a positive MRI (PI-RADS scores 3-5) also points to an abnormality likely to represent clinically significant cancer. However, not all significant cancers are found after targeted biopsies only, and systematic biopsies are additionally recommended by multiple urological guidelines. This means that different combinations and sequencing of diagnostic tests can be done, each of which has been proposed as a pathway.