Landmark multisite sequencing studies of mCRPC have uncovered complex patterns and mechanisms of seeding (7, 15), phenotypic heterogeneity (16), and significant androgen receptor (AR) genomic complexity (7, 17), a striking finding considering that lethal prostate cancer has passed through at least two evolutionary bottlenecks: acquisition of metastatic potential and development of castration resistance. The gene discussed is AR; the disease is prostate cancer.