The National Comprehensive Cancer Network® (NCCN®) has updated its Clinical Practice Guidelines in Oncology, recognizing circulating tumor DNA (ctDNA) as a high-risk factor for recurrence in colon and rectal cancers. It is also stated it is useful for assessing disease burden in Merkel cell carcinoma, often detectable before clinical recurrence. However, ctDNA is deemed prognostic, not predictive, for adjuvant treatment in colon cancer, and routine use is not recommended outside clinical trials. Similarly, in rectal cancer, ctDNA is a prognostic marker post-local excision but lacks sufficient evidence for routine use.