Background: Diagnosis of small foci of prostate cancer in a core biopsy is one of the major diagnostic challenges. Immunohistochemistry plays an important role in the diagnosis of minimal prostate cancer and to exclude the benign lesions. The __ampersandsignalpha;-methylacyl CoA racemase (AMACR) and p63 have been used for such purpose. Aim of work: To investigate which basal cell marker; 34__ampersandsignbeta;E12 or p63 should be the first choice used with AMACR to increase diagnostic accuracy of minimal prostate cancer in core biopsy, in a trial to reduce the errors in diagnosis and to decrease the need for repeated biopsies. Methods: Sections from formalin-fixed paraffin-embedded tissues of 60 prostate needle biopsy specimens were stained immunohistochemically with 34__ampersandsignbeta;E12, p63, Ki-67 and AMACR. Results: AMACR was expressed in 90% of minimal prostatic carcinoma. Nuclei of basal cells in 90% of normal glands were stained for p63. Regarding 34__ampersandsignbeta;E12, all benign subjects showed linear cytoplasmic basal staining. 34__ampersandsignbeta;E12 had very high sensitivity and specificity values (96.3% and 100%, respectively), followed by p63 (97.9% and 85.3%). There were significant differences in cytoplasmic p63 expression between benign tissue and prostate cancer, and between low and high grade carcinoma (P __ampersandsignlt;0.001). It was also found that higher levels of cytoplasmic p63 were significantly associated with higher frequency of proliferating cells. Conclusions: Combined assessment of 34__ampersandsignbeta;E12 and p63 as a negative (cytoplasmic and nuclear, respectively) marker and AMACR as a positive marker for identifying prostate adenocarcinoma could greatly improve the diagnosis of minimal prostate cancer in needle biopsy specimens.