Gupta and colleagues report in Prostate Cancer and Prostatic Diseases (PCAN) the characterization of Androgen Receptor (AR) null metastatic castration-resistant prostate cancer (AR null mCRPC) using a novel immunohistochemical assay combined with AR genotyping as part of the MSK-Impact next-generation sequencing panel at Memorial Sloan Kettering Cancer Center. Patients were selected to have non-neuroendocrine prostate cancer (NEPC) in order to identify a subgroup of adenocarcinoma patients that have lost AR expression. Such findings could identify those men less likely to benefit from AR inhibitors and who may benefit from alternative approaches. In this retrospective study of 26 men with mCRPC who underwent sequencing and AR IHC, 5 patients (19%) demonstrated loss of AR protein expression, which is in line with prior autopsy and mCRPC genomic survey studies of the prevalence of NEPC-like biomarkers in this setting.