Imperiale TF, Kisiel JB, Itzkowitz SH, et al. - In an average-risk screening population of 45 to 49 year-olds, researchers sought to determine the specificity of the multitarget stool DNA (mt-sDNA) test for colorectal cancer screening. There were 816 participants in the evaluable cohort, out of 983 registered candidates, with a mean age of 47.8 (SD, 1.5) years and 47.7% were women. No participants in the evaluable cohort had colorectal cancer, while 49 had advanced precancerous lesions (APL), 253 had nonadvanced adenomas (NAA), and 514 had negative colonoscopic findings. According to this prospective cross-sectional study, sensitivity for APL was 32.7%, with most APL (83.7%) measuring 10–19 mm and none having high-grade dysplasia. Data reported that the area under the ROC curve for distinguishing between APL and lesser findings was 0.72. The high specificity of mt-sDNA will help reduce risk in this age group from unnecessary diagnostic procedures. This investigation reveals that mt-sDNA has high specificity among average-risk 45 to 49-year olds, promoting its use as a noninvasive alternative for colorectal cancer screening.