Genomic profiling of tumours in cancer patients can help to identify molecular alterations associated with disease progression and resistance to therapy, and therefore provide information that may be relevant to patient management. However, it can be technically difficult or even dangerous to repeatedly access lesions in certain anatomical sites, and the inherent heterogeneity of tumours means that a biopsy may not reflect all clones within the tumour cell population. The knowledge that tumours release nucleic acids into the circulation has given credence to the idea of a blood test or “liquid biopsy” as a promising alternative to current clinical practices for the serial detection of disease-associated genetic changes in cancer patients. We are investigating the potential of exosomes (nano-sized extracellular vesicles which contain a molecular signature similar to their cell of origin) as a source of tumour DNA for monitoring patient response to chemotherapy. We hypothesised that (1) exosomes isolated from the blood of cancer patients contain DNA in which tumour-specific mutations can be detected; and (2) monitoring the genomic profiles of exosomes will facilitate earlier identification of disease progression. In a case study of a patient with metastatic breast cancer, we show that: (1) genetic variants can be identified in the exoDNA isolated from blood taken at diagnosis; (2) these variants became undetectable in patient exoDNA following months of intensive chemotherapy (reflecting treatment response); and (3) new exoDNA variants were identified in a subsequent sample that pre-dated the development of brain metastases within the patient (indicative of clonal re-emergence). We are currently testing our findings in a larger cohort of breast cancer patients, and anticipate that this approach will provide a more sensitive and specific method for cancer monitoring than current modalities.