BACKGROUND The prostatic neuroendocrine cell is a regulatory cell that produces serotonin and peptide hormones. This cell is part of a more widely dispersed diffuse neuroendocrine regulatory system known as the APUD system. Focal neuroendocrine differentiation is seen in virtually all prostate carcinomas to one degree or another. Specific malignancies that are purely neuroendocrine include small cell carcinoma and carcinoid/carcinoid-like tumors. A variety of studies suggest a possible prognostic significance of neuroendocrine differentiation in prostate carcinoma. METHODS The literature on the prostatic neuroendocrine cell and neuroendocrine differentiation in prostate carcinoma is reviewed. RESULTS Based on analogy with other better studied elements of the diffuse neuroendocrine regulatory system or APUD system, as well as the morphology and specific products produced by neuroendocrine cells, it is likely that they play an important regulatory role in the prostate. Neuroendocrine differentiation may be of prognostic significance in prostate carcinoma. Mechanisms are not well characterized at this point, but the known growth factor activity of the neuroendocrine cell products, an increase in proliferation in cells surrounding neuroendocrine cells, and a lack of androgen receptor expression in neuroendocrine cells, suggest mechanisms by which they may be of prognostic significance. CONCLUSIONS Neuroendocrine differentiation in prostate carcinoma may be of prognostic significance, but better methods to define neuroendocrine, differentiation are necessary. The therapeutic implications of neuroendocrine differentiation in prostate carcinoma may be of significance and need to be explored further.