Prostate cancer is the most prevalent form of cancer in western men. An accurate early localization of prostate cancer, permitting efficient use of modern focal therapies, is currently hampered by a lack of imaging methods. Several methods have aimed at detecting microvascular changes associated with prostate cancer with limited success by quantitative imaging of blood perfusion. Differently, we propose contrast-ultrasound diffusion imaging, based on the hypothesis that the complexity of microvascular changes is better reflected by diffusion than by perfusion characteristics. Quantification of local, intravascular diffusion is performed after transrectal ultrasound imaging of an intravenously injected ultrasound contrast agent bolus. Indicator dilution curves are measured with the ultrasound scanner resolution and fitted by a modified local density random walk model, which, being a solution of the convective diffusion equation, enables the estimation of a local, diffusion-related parameter. Diffusion parametric images obtained from five datasets of four patients were compared with histology data on a pixel basis. The resulting receiver operating characteristic (curve area = 0.91) was superior to that of any perfusion-related parameter proposed in the literature. Contrast-ultrasound diffusion imaging seems therefore to be a promising method for prostate cancer localization, encouraging further research to assess the clinical reliability.