A new prospective national study, CUP-COMP, is testing whether a blood-based molecular profiling approach can identify cancers of unknown primary by detecting molecular signals released by tumors into circulation. The initiative targets a population in which metastatic disease is present but the tissue of origin remains unidentified. CUP-COMP evaluates the potential of a blood test to narrow diagnostic uncertainty, potentially enabling earlier matching to targeted and tissue-agnostic treatment strategies. The study design is positioned as an attempt to convert ctDNA or related circulating signals into actionable clinical information. For oncology stakeholders, the trial adds to a growing push toward liquid biopsies that can resolve diagnostic gaps when conventional imaging and pathology cannot localize the primary tumor. Key outcomes to watch include sensitivity, specificity, and whether results lead to changes in treatment selection and improved patient management decisions.