A large-scale study has for the first time reported the high degree of interfocal genomic heterogeneity in multifocal primary prostate cancer, which could inform clinical decision-making. Whole-exome sequencing in 89 tumour foci from 41 patients revealed that 76% of matched foci from the same prostatectomy specimen had no common somatic point mutations and that DNA copy number alterations were rarely shared among foci. Although a small number of mutations were shared across foci, they rarely occurred in driver genes.