Needle biopsy of the prostate safely furnishes tissue that can be studied for the effects of promising chemopreventive agents on biomarkers. The modulation of biomarkers, such as those for apoptosis (TUNEL, Bcl-2, or nuclear morphometry), angiogenesis (factor 8), and cell proliferation (Ki-67), can indicate the potential of a new agent without waiting for the definitive evaluation of traditional endpoints, such as reduction in cancer mortality. A recent modification of prostate biopsy technique, including additional cores taken from the lateral peripheral zone, may improve the cancer yield by as much as 35% without increasing major complications, facilitating serial in vivo tests on cancer tissue. The serial biopsy approach may be especially valuable in "watchful waiting" cohorts.