The use of serum prostate-specific antigen screening to facilitate early detection of prostate cancer has resulted in a dramatic increase in the number of prostate needle core biopsies which pathologists must examine. This has been accompanied by a strong increase in the number of biopsies with ambiguous lesions, and an unequivocal diagnosis of malignancy is difficult to render, especially in the case of limited foci or in small atypical acinar lesions. When assessing small foci of atypical glands upon needle biopsy, the pathologist searches for differences between the benign glands and atypical glands in terms of usual morphological features and in such cases, immunohistochemical stains for basal cell markers such as 34betaE12 antibody or antibodies directed against cytokeratin 5 and 6 and more recently p63 may be a useful adjuvant to identify basal cells which are typically present in benign glands but absent in prostatic carcinoma. However several benign mimickers of prostate carcinoma, including atrophy, atypical adenomatous hyperplasia, nephrogenic adenoma can stain negatively with these antibodies and thus a negative basal cell marker immunostain alone does not exclude a diagnosis of benignancy. Alpha-methyl-coenzyme-A-racemase (AMACR) a new sensitive marker of prostate carcinoma, can be useful in confirming ambiguous lesion suspected for malignancy. Although, as with any immunohistochemical studies, problems exist in terms of both sensitivity and specificity. The aim of this review is to describe the histological features of prostatic carcinoma in case of small focus, and discuss the application of these new prostatic markers in the light of the current literature to highlight the best practice guidelines.