OBJECTIVES: To estimate the required spatial alignment accuracy for correctly grading 95 \% of peripheral zone (PZ) prostate cancers using a system for multiparametric magnetic resonance (MR)-guided ultrasound (US) biopsies. METHODS: PZ prostate tumours were retrospectively annotated on multiparametric MR series using prostatectomy specimens as reference standard. Tumours were grouped based on homogeneous and heterogeneous apparent diffusion coefficient (ADC) values using an automated ADC texture analysis method. The proportion of heterogeneous tumours containing a distinct, high Gleason grade tumour focus yielding low ADC values was determined. Both overall tumour and high-grade focal volumes were calculated. All high-grade target volumes were then used in a simulated US biopsy system with adjustable accuracy to determine the hit rate. RESULTS: An ADC-determined high-grade tumour focus was found in 63 \% of the PZ prostate tumours. The focal volumes were significantly smaller than the total tumour volumes (median volume of 0.3 ml and 1.1 ml respectively). To correctly grade 95 \% of the aggressive tumour components the target registration error (TRE) should be smaller than 1.9 mm. CONCLUSIONS: To enable finding the high Gleason grade component in 95 \% of PZ prostate tumours with MR-guided US biopsies, a technical registration accuracy of 1.9 mm is required. KEY POINTS : AC/a,!AC/ MRI can identify foci of prostatic cancer with reduced apparent diffusion coefficients AC/a,!AC/ Sixty-three per cent of prostatic peripheral zone tumours contain high-grade tumour low ADC foci AC/a,!AC/ The median volume of such foci is 0.3 ml AC/a,!AC/ Biopsy targets are significantly smaller than whole tumour volumes AC/a,!AC/ Simulated registration accuracy is 1.9 mm for correctly grading 95 \% of tumours.