In recent years, attention has focused on the prognostic importance of neuroendocrine differentiation in prostate cancer. Focal neuroendocrine differentiation in prostatic adenocarcinoma is a frequent finding. Though controversial, the prevalence of neuroendocrine cells has been correlated with higher-grade malignancy and poor prognosis. As with other small cell tumors, production of ectopic neuropeptides has been reported. The rarity of the disease has precluded prospective randomized trials. Therapeutic regimens have mainly been modeled after those for small cell lung carcinoma. Here we review the literature to identify potential diagnostic, therapeutic, and prognostic factors. Evident from this review is the necessity for further research in the biology of small cell carcinoma progression, in order to improve therapy.