Several recent studies have focused attention on neuroendocrine differentiation (NED) in prostatic carcinoma (PC). Clinical studies have shown PC with NED to behave aggressively and to be associated with poor prognosis. To evaluate NED as an independent prognostic factor, we conducted a retrospective study of 87 patients with clinically localized PC who underwent radical prostatectomy. The presence of neuroendocrine tumor cells was confirmed by positive immunostaining for serotonin, chromogranin A, and neuron-specific enolase. The correlation between NED and disease progression was assessed. Progression of cancer was demonstrated in 35 (40%) of the patients. The presence of NED was confirmed in 60 (69%) of cases, and of these patients 26 (43%) manifested evidence of disease progression. Disease progression was also manifest in nine (33%) of the 27 patients without evidence of NED. Thus, in the setting of clinically localized carcinoma of the prostate, NED does not appear to be a statistically significant independent prognostic factor.