Aim: We hypothesize that the combination of T2-weighted (T2W) MRI with diffusion-weighted imaging (DWI) methods provides a powerful clinical application for the differential diagnosis of prostate cancer and benign lesion in the prostatic transition zone (TZ). Methods: This retrospective study included 113 patients who were diagnosed with TZ lesions by MRI. The apparent diffusion coefficient values were compared between biopsy-proven benign and malignant lesions. Results: The apparent diffusion coefficient values for the malignant nodules were significantly lower than those of the benign nodules. The area under the curve values for T2W imaging combined with DWI and T2W imaging alone were 0.991 and 0.884, respectively. Conclusion: T2W combined with DWI provides a powerful tool for noninvasive differentiation between malignant and benign prostatic hyperplasia nodules in the prostatic TZ.