To compare the performance of diffusion-weighted imaging-guided transitional zone (TZ) lesion scoring on T2-weighted imaging (DWI-guided TZ scoring) to conventional PI-RADS TZ scoring. Forty patients carried transition zone prostate cancer (TZPCa), and 40 patients had benign prostatic hyperplasia without TZPCa. A lesion-base, one-to-one correlation between the pathologic mapping sheet and the corresponding MR imaging was conducted by consensus between the genitourinary-specialized radiologist and pathologist. DWI-guided TZ scoring was defined as evaluating the DWI/apparent diffusion coefficient (ADC) images first, identifying the suspicious foci, then correlating the foci with the T2-weighted imaging, and finally assigning the PI-RADS score based on PI-RADS v2.1. Three other radiologists independently recorded the PI-RADS v2.1 scoring for TZ and the DWI-guided TZ scoring, with a time interval of 4weeks. When a PI-RADS score of ≥ 3 was considered a positive lesion, the specificity, PPV, NPV and sensitivity between the DWI-guided TZ scoring and conventional PI-RADS TZ scoring were 0.896 vs. 0.542 (p < .001), 0.764 vs. 0.439 (p < .001), 0.853 vs. 0.759 (p = .001), and 0.687 vs. 0.676 (p = .836), respectively. When PI-RADS scores ≥ 4 was considered cancer-positive, the specificity and PPV were also higher when applying DWI-guided TZ scoring (0.986 vs. 0.944, p = .007; 0.943 vs. 0.810, p = .009, respectively); however, the sensitivity and NPV were not statistically different (0.468 vs. 0.468, p = .998; 0.785 vs. 0.776, p = .537, respectively). The interobserver agreement presented as κ-value was higher in DWI-guided TZ scoring (0.584) than in conventional PI-RADS TZ scoring (0.155) (p = .003). DWI-guided TZ scoring improves the interobserver agreement, specificity, and predictive value without impairing the sensitivity.