Since the introduction of immunohistochemistry, there is an increasing interest in neuroendocrine (NE) differentiation in prostatic carcinomas. Focal NE differentiation in prostatic adenocarcinomas is a very frequent finding. It is subject of numerous studies, since a negative impact on prognosis and an important role in antiandrogen therapy failure are suspected. NE-differentiated small-cell carcinoma is a very rare tumor comprising 0.5-2% of all prostatic carcinomas. Nevertheless, although very rare, it is of clinical importance because it is one of the most aggressive tumors of the prostate with a very poor prognosis. This review is focused on actual concepts of histogenesis, cell biology, clinical implications, and possible future therapeutic perspectives of these two tumor entities.