Recent data suggest that PSA expression can be directly influenced by some factors, independently from the variation in prostate cell growth. Some growth factors such as fibroblast growth factor, transforming growth factor beta and epidermal growth factor, seem to be directly involved in the regulation of mRNA-PSA expression, whereas androgens could have an indirect activity. On the basis of these experimental data, this review tries to analyze some limits of PSA and some recent data on the role of PSA-isoforms, in particular in the follow-up of prostate cancer patients submitted to radical prostatectomy or hormone-therapy. Moreover, relevant informations can be obtained analyzing the variance of PSA in patients submitted to intermittent androgen deprivation.