The continued high mortality toll from cancer reflects, in part, the inability to provide comprehensive screening for the entire at-risk population. The ideal cancer screening test not only needs to be highly accurate but also must foster patient compliance in that discomfort, embarrassment, and expense present formidable barriers to screening. Of the myriad modalities currently available (eg, radiography and endoscopy), serum biomarkers hold the greatest promise with regard to patient acceptability.1 Biomarkers generally identify the presence of malignancy by means of (1) circulating tumor components, (2) proteins elaborated by tumor, or (3) host response to the tumor (eg, immunologic). To date, the most commonly used serum screening tests (such as α-fetoprotein, CA-125, and prostate-specific antigen for hepatocellular, ovarian, and prostate cancer, respectively) have generally focused on the former 2 categories. However, these tests have many problems, including low sensitivity for early-stage, curable cancers. Moreover, modest specificity, coupled with low disease prevalence, translates into a low positive predictive value. Therefore, most positive test results may actually be false-positive, thereby resulting in numerous unnecessary invasive procedures, which in turn can lead to anxiety, discomfort, and cost.2 Clearly, more accurate serum biomarkers are urgently needed.