Introduction This study aimed to investigate the relationship between the serum PSA level, Gleason score (GS), PI-RADS v2 score, tumor ADC(min) value, and the largest tumor diameter in patients that underwent radical prostatectomy (RP) due to prostate cancer (PCa) and to comparatively evaluate the variables of these parameters in clinically significant and insignificant PCa groups. Materials and methods The mpMRI examinations of the patients who underwent RP due to PCa were retrospectively evaluated. According to the final GS, the lesions were divided into two groups as clinically significant (GS >= 7) and insignificant (GS <= 6). The PSA value, tumor ADC(min) value, tumor diameter, and PI-RADS score were compared between the clinically significant and nonsignificant PCa groups using Student's t-test. The correlations between the serum PSA level, GS, PI-RADS v2 score, tumor ADC(min) value, and tumor diameter were evaluated separately (Pearson's correlation analysis was used for peripheral gland tumors, and Spearman's correlation analysis for central gland tumors). A ROC analysis was undertaken to evaluate the efficacy of the tumor ADC(min), diameter and PSA values in differentiating clinically significant and nonsignificant tumors. Results In both central and peripheral gland tumors, there was a correlation between the PSA level, tumor diameter, PI-RADS score, ADC(min) value, and GS at various levels (poor, moderate, and high). In central gland tumors, there was no significant difference between the two groups in terms of the PSA value and PI-RADS scores (p > 0.05), but the ADC(min) value and diameter of the tumor significantly differed (p < 0.05). For peripheral gland tumors, significant differences were observed in all parameters (p < 0.05). The cut-off values for the peripheral and central gland tumors are as follows: lesion diameter, 13.5 mm and 19 mm; tumor ADC(min), 0.709 x 10(-3) mm(2)/s and 0.874 x 10(-3) mm(2)/s; and PSA level, 8.47 ng/ml and 11.10 ng/ml, respectively. Conclusion The current PI-RADS v2 scoring system can be inadequate in distinguishing clinically significant and insignificant groups in central gland tumors. A separate cut-off value of the tumor diameter should be determined for central and peripheral gland tumors. Tumor ADC(min) values can be used as a predictive parameter. The PSA cut-off value should be kept lower in peripheral gland tumors.