The American Cancer Society updated colorectal cancer screening guidance in CA: A Cancer Journal for Clinicians, reaffirming a diversified testing strategy while emphasizing an expanded menu of at-home options. The update addresses a rising trend in early-onset colorectal cancer among adults under 65, retaining the lower screening start age of 45 for average-risk individuals. The guidance continues to include colonoscopy as the “gold standard” and CT colonography, alongside stool-based testing. It also adds newer at-home multi-target stool tests, including next-generation mt-sDNA and mt-sRNA assays as well as hemoglobin-based approaches, with evidence presented that the newer mt-sRNA and updated mt-sDNA options show similar accuracy to the original multi-target stool test. Blood-based screening approaches demonstrated lower sensitivity for advanced precancer and stage I cancers and remain non-preferred compared with stool-based strategies. The report also stresses that clinical benefit depends on timely follow-up, including colonoscopy ideally within six months of a positive result.