AR and adenocarcinoma: While prostate cancer typically arises as an androgen receptor (AR)-driven adenocarcinoma, reflecting its luminal prostate cell of origin1, up to 15–20% of castration resistant prostate cancer (CRPC) tumors acquire alternative lineage programs as a mechanism of treatment resistance including transformation to a poorly differentiated small cell/neuroendocrine prostate cancer (NEPC) with loss of AR-dependence and morphologic features often indistinguishable from small cell carcinomas arising from other sites2–4.