Reports on neuroendocrine prostate cancer (NEPC) are scarce and mostly based on historical series or case reports. Importantly, incidence rates and survival figures of NEPC in contemporary patients are unknown. A retrospective analysis from a large administrative database was used to answer this question. NEPC is rare and mostly diagnosed at metastatic stage. Prognosis is poor regardless of histologic subtype. Introduction Neuroendocrine carcinoma of the prostate (NEPC) is a rare entity. We aimed at providing contemporary data on incidence and survival figures of de-novo NEPC. Materials and Methods Within the Surveillance, Epidemiology, and End Results (SEER) database, we identified 309 individuals with de-novo NEPC diagnosed between 2004 and 2013. We evaluated age-adjusted incidence rates over the study. Kaplan-Meier analyses assessed overall survival (OS) after stratification according to histologic subtype, metastatic status, and treatment. Cox regression analyses tested the predictors of overall mortality, after adjusting for confounders. Results A total of 309 cases of NEPC were identified from 510,913 cases of prostate cancer. Metastatic disease was identified in 198 (64.1%) cases. The most common histologic subtype (n = 186; 60.2%) was small-cell carcinoma (SCC). The age-adjusted incidence of NEPC significantly increased over the study span. However, this increase only affected SCC (from 0.13/1,000,000 person-years in 2004 to 0.30/1,000,000 person-years in 2013; P = .001). Median survival for NEPC was 10 months. After stratification by metastatic status, no difference was observed according to SCC versus non-SCC. Treatment with radical prostatectomy improved OS only among individuals with non-metastatic disease, whereas radiation therapy did not affect OS rates. In multivariable Cox regression analyses predicting overall mortality, metastatic stage (hazard ratio, 1.52; 95% confidence interval, 1.12-2.06; P & #x003C; .01) and radical prostatectomy (hazard ratio, 0.38; 95% confidence interval, 0.20-0.74; P & #x003C; .01) achieved independent predictor status. Conclusion De-novo NEPC is extremely rare and will be encountered in clinical practice by few urologists. Most cases are metastatic at diagnosis. Prognosis is poor regardless of histologic type, especially in metastatic stage. © 2017 Elsevier Inc.