The emergence of molecular analysis approaches that use circulating tumor DNA (ctDNA) to measure minimal residual disease is shifting the management of colorectal cancer and many solid tumor cancers. Analysis of ctDNA has several advantages: It is less invasive than an open biopsy; serial testing can occur; it may be more representative of the whole tumor, including metastatic sites; and it can provide a quantitative analysis of tumor burden. Nurses can help educate the patient and family about ctDNA testing in cancer management, assist in collecting blood, monitor test results, participate in interprofessional collaboration of care, and advocate for coverage of testing.