To improve our clinical management of AR-negative mCRPC, new therapies and molecular biomarkers are needed, which hinge on the development and study of a wide range of prostate cancer models that recapitulate the broad spectrum of clinicopathological features associated with all mCRPC variants, including AR-negative adenocarcinoma, NEPC, DNPC and mixed/heterogeneous morphologies. The gene discussed is AR; the disease is prostate cancer.