After long-term androgen deprivation therapy, 25-30% prostate cancer (PCa) acquires an aggressive neuroendocrine (NE) phenotype. Dysregulation of YAP1, a key transcription coactivator of the Hippo pathway, has been related to cancer progression. However, its role in neuroendocrine prostate cancer (NEPC) has not been assessed. Immunohistochemistry and bioinformatics analysis were conducted to evaluate YAP1 expression levels during PCa initiation and progression. YAP1 expression was present in the basal epithelial cells in benign prostatic tissues, lost in low-grade PCa, but elevated in high-grade prostate adenocarcinomas. Interestingly, the expression of YAP1 was reduced/lost in both human and mouse NEPC. The expression of YAP1 is elevated in high-grade prostate adenocarcinomas but lost in NEPC.