Phenotypic plasticity associated with epithelial to mesenchymal transition occurs in the late stage of several types of cancers and results in metastatic spread and enhanced resistance to therapy. Understanding these events is important to prevent and cure this aberrant conversion. Intriguingly, primary prostate tumors are androgen-sensitive and display a strong luminal identity. In contrast, aggressive prostate tumors are characterized by change of identity, insensitivity to androgen ablation therapy. Thus, an active mechanism maintains the normal physiologic androgen responsive status preventing plasticity. In this study, we show for the first time that conditional knockout of the epithelial specific ETS factor EHF/ESE3, which is a top ranking expressed TF in the normal prostate, is sufficient to determine a dramatic loss of cell identity and transformation. Bulk and single-cell RNA sequencing revealed that loss of EHF/ESE3 reactivates an aberrant ambiguous cell program with acquisition of endothelial and stromal features. Astonishingly, crossing the cEHF-KO mice with TMPRSS2-ERG mice resulted in complete conversion of the epithelial component to a stromal like status supported by tracing the epithelial cells TMPRSS2ERG/eGFP positive. Notably, integration of data from prostate cancer patients’ datasets supports that cEHF-KO and cEHF-KO/R26ERG recapitulate stem cell like and neuroendocrine prostate tumors and that are enriched of cancer stem cell-like cells.