The aim of this work was to determine the potential of diffusion weighted magnetic resonance imaging (DW-MRI) for identifying prostate cancer by comparing apparent diffusion coefficients (ADCs) from malignant peripheral zone (PZ) nodules with values from the non-malignant PZ and the predominantly benign central gland (CG). 33 patients with elevated prostate specific antigen (PSA) aged 52-78 years (30 patients with biopsy proven prostate cancer) underwent endorectal MRI with T2 weighted and echo planar diffusion weighting (b = 0 mm2 s(-1), 300 mm2 s(-1), 500 mm2 s(-1) and 800 mm2 s(-1)) sequences. ADCs were measured from 30 malignant PZ nodules (identified on T2 weigting and positive biopsy; median region of interest (ROI) size 41 mm2), 33 CG regions (predominantly benign nodules; median ROI size 218 mm2) and 18 non-malignant PZ regions (ipsilateral biopsies all benign; median ROI size 54.5 mm2). ADCs were (mean+/-standard deviation (SD); mm2 s(-1)): malignant PZ nodules 1.30+/-0.30x10(-3), CG 1.46+/-0.14x10(-3) and non-malignant PZ 1.71+/-0.16x10(-3). Differences between all three groups were statistically significant (p = 0.01 malignant PZ vs CG; p = 0.0001 malignant PZ vs non-malignant PZ and p = 0.0001 CG vs non-malignant PZ). Using receiver operating characteristic curves, cut-off values of 1.39x10(-3) mm2 s(-1) differentiated malignant PZ nodules from predominantly benign CG (sensitivity 60%, specificity 76%) and of 1.6x10(-3) mm2 s(-1) identified malignant from non-malignant PZ (sensitivity 86.7%, specificity 72.2%). These results suggest that DW-MRI has the potential to increase the specificity of prostate cancer detection because ADCs are significantly lower in malignant compared with non-malignant prostate tissue.