It has been suggested that in multifocal prostate cancer (PCa), focal therapy to the largest (index) lesion is sufficient, because secondary non-index lesions are unlikely to contribute to disease progression. In this study, the role of PCa focality in selecting men for focal therapy was evaluated. A histopathological analysis of the index and non-index lesions of 100 consecutive radical prostatectomy specimens was carried out. Cases that would have been suitable for focal ablation were also evaluated. Tumours were more often multifocal (78%) and bilateral (86%). In total, 270 tumour foci were identified. In multifocal disease, tumour volume, Gleason score and pathological stage were almost invariably defined by the index lesion of the specimen; among the 170 satellite foci, 148 (87%) were <0.5 cm(3) and 169 (99.4%) had Gleason score ≤ 6. Using the defined criteria, 51% of men in this series would have been considered suitable for focal ablation of the index lesion. Histological features of poor prognosis in the prostate are associated with the index lesion. There is a high proportion of patients who may be suitable for focal therapy, and clinical trials of index lesion ablation should be considered as part of this therapeutic strategy.