Throughout the past 20 years, a prostate cancer screening pathway has been constructed and refined to diagnose prostate cancer. Although one primary pathway for screening prostate cancer has been developed and refined within the past 20 years, there remain many problems with this pathway, including a general lack of sensitivity and specificity; an inability to diagnose the progression of the disease; a significant risk presented to screening patients resulting from confirmatory diagnostic testing; and a lack of evidence supporting the reduction in prostate cancer mortality resulting from screening. Moreover, current screening methods are becoming an increasingly significant health care cost, accounting over $1.8 billion for the Prostate Specific Antigen (PSA) test alone in the United States each year. To address these problems, this study provides a review of both current and emerging literature regarding prostate cancer screening methods. Comparative criteria were defined and integrated into a quantitative cost effectiveness (CE) model to evaluate the effectiveness of each screening method examined in the literature search more comprehensively. Overall, the Alpha-Methylacycl Coenzyme A Racemase (AMACR) urine-based biomarker test, followed by a biopsy, was found to be the most cost-effective screening method.