A next-generation sequencing analysis of circulating tumour DNA (ctDNA) from 442 patients with cancer of unknown primary (CUP) has revealed the presence of at least one detectable alteration in 79.9% of patients, of which 89.6% of alterations were potentially targetable through off-label use of FDA-approved agents. Furthermore, investigators were able to monitor dynamic changes in the presence of specific mutations over time in ctDNA from blood samples taken at various time points in the treatment of two selected patients. These findings demonstrate the potential of liquid biopsy approaches in the delivery of targeted therapies to patients with CUP.