It has been shown that prostatic adenocarcinoma differentiation correlates with prostatic-specific marker and neuroendocrine expression; that is, the more undifferentiated the tumor, the less it expresses prostatic markers and the more neuroendocrine cells are found in it. Complete absence of prostatic markers together with marked neuroendocrine expression has been associated with small cell morphology. This report describes a case of a metastatic, prostatic marker-negative, non-small cell prostatic adenocarcinoma with a prominent neuroendocrine component. The architecturally well-organized luminal-exocrine cells appeared ultrastructurally undifferentiated, however, displaying an almost empty cytoplasm. This contrasted with the prostatic marker-positive control cases of prostatic carcinoma, which contained relatively numerous cytoplasmic vacuoles. The neuroendocrine cells could be identified by light microscopy as eosinophilic cells. The number of the latter cells was markedly increased in the metastatic foci compared with the primary tumor. Light microscopically and ultrastructurally, the eosinophilic cells in this case differed from the Paneth-like cells described in prostatic carcinoma in previous reports. This case provides support for the general concept of multidirectional differentiation in human epithelial cancers and in particular for the association of poor tumor differentiation with neuroendocrine expression in prostatic carcinoma. In addition, in contrast with previous reports describing absence of basement membrane in metastatic foci of prostatic carcinoma, in the current case well-formed basal laminae were identified.