Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer. Clinical Context Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection. Recent Data Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic. Results In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern. Provisional Clinical Opinion On the basis of identified evidence and the expert opinion of the panel ( Table 1 provides a description of how recommendations and evidence are rated): In men with a life expectancy ≤ 10 years,* it is recommended that general screening for prostate cancer with total PSA be discouraged, because harms seem to outweigh potential benefits. Type and strength of recommendation. Evidence based: strong. Strength of evidence. Moderate: based on five randomized clinical trials (RCTs) with intermediate to high risk of bias, moderate follow-up, and limited data on subgroup populations. In men with a life expectancy > 10 years,* it is recommended that physicians discuss with their patients whether PSA testing for prostate cancer screening is appropriate for them. PSA testing may save lives but is associated with harms, including complications, from unnecessary biopsy, surgery, or radiation treatment. Type and strength of recommendation. Evidence based: strong. Strength of evidence. For benefit, moderate; for harm, strong: based on five RCTs (and several cohort studies) with intermediate to high risk of bias, moderate follow-up, indirect data, inconsistent results, and limited data on subgroup populations. It is recommended that information written in lay language be available to clinicians and their patients to facilitate the discussion of the benefits and harms associated with PSA testing before the routine ordering of a PSA test. Type and strength of recommendation. Informal consensus: strong. Strength of evidence. Indeterminate: evidence was not systematically reviewed to inform this recommendation; however, randomized trials are available on the topic. *Calculation of life expectancy is based on a variety of individual factors and circumstances. A number of life expectancy calculators (eg, http://www.socialsecurity.gov/OACT/population/longevity.html) are available in the public domain; however, ASCO does not endorse any one calculator over another. NOTE. ASCO PCOs reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and settings for further research. Because of the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical practice and cannot be assumed to apply to the use of these interventions in the context of clinical trials. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO PCOs or for any errors or omissions.