OBJECTIVES: Neuroendocrine (NE) differentiation in prostate cancer is believed by some authors to play an important role in the development of androgen resistance. However, there is little knowledge about the impact of short-term neoadjuvant hormonal therapy on NE differentiation and on whether the degree of tumor regression is linked with the extent of NE differentiation. METHODS: NE cells were detected by immunohistochemistry using a chromogranin A antibody. The densities of NE cells in 20 pretreated and 20 nonpretreated radical prostatectomy specimens were compared. Furthermore, we compared the NE cell density in tumors with variable degrees of regression. RESULTS: The median percentage of tumor cells showing NE differentiation did not significantly differ between pretreated and nonpretreated specimens (0.61%, range 0.0-2.4%, vs. 1.47%, range 0.0-6.8%; p = 0.9896). Twelve nonregressive/slightly regressive tumor foci and 12 strongly regressive tumor foci were assessed. The NE cell density did not differ significantly (p = 0.1227). CONCLUSIONS: Short-term neoadjuvant hormonal therapy does not induce relevant clonal propagation of NE cells. The degree of tumor regression following short-term neoadjuvant hormonal therapy does not correlate with the extent of NE differentiation.