BACKGROUND Neoadjuvant androgen deprivation in prostate cancer induces tumor volume regression but does not improve outcome of the patient. A possible explanation for this phenomenon could be an increase of the residual tumor aggressiveness brought about by antiandrogen therapy. The purpose of the present study was to evaluate the frequency of tumor dedifferentiation following androgen blockade in prostate cancer and to determine if the remaining tumor shows signs of increased aggressiveness. METHODS Thirty patients bearing locally advanced prostate cancer (stages T2c - T3) were submitted to neoadjuvant anti-androgenic therapy during four months followed by radical prostatectomy. Gleason scores from biopsy and surgical specimens were compared. Furthermore, the cell proliferation index was evaluated by immunohistochemistry assay for PCNA, tests with strong nuclear staining were considered positive. The percentage of positive nuclei, counted in 500 cells, was determined in several categories of the Gleason score from surgical specimens. RESULTS In 11(37%) surgical specimens the Gleason score was equal or lower than that found in the biopsy and in 19 (63%) the total score was higher in the surgical specimens (p<0.05). The median of PCNA expression was 4.5%, 10%, 12% and 14% in Gleason scores 2-4, 5-6,7 and 8-10, respectively (p>0.05). The median of cell proliferation indexes was 9% for glandular or specimen confined tumors and was 17% for extraprostatic tumors (p<0.05). CONCLUSION The lower Gleason score was found in almost 2/3 of patients submitted to antiandrogen therapy. However, the cell proliferation index measured by PCNA was the same for tumors with lower or higher Gleason scores. It seems that cell dedifferentiation seen after neoadjuvant androgen deprivation represents a mere morphologic phenomenon and not a real increase in tumor aggressiveness.