One of the major drawbacks for disease monitoring in patients with solid cancer is the inability to obtain representative tumour samples. It can be technically difficult and even dangerous to access lesions in certain sites, and if a tumour biopsy is obtained the heterogeneous nature of the disease means that the sample may not be characteristic of the entire tumour cell population. As tumour-derived exosomes (TEX) contain a molecular signature specific to their cell of origin and can be collected from the blood in a relatively non-invasive manner, a ‘liquid biopsy’ approach is seen to be advantageous over current clinical practices as it is less invasive than traditional biopsies and is thought to more accurately reflect the total disease burden in cancer patients. While much attention is placed on characterizing TEX proteins and RNA, little work has been done to investigate the clinical applications of exosomal DNA (exoDNA). We hypothesised that (1) TEX isolated from the blood of cancer patients contain DNA in which tumour-specific mutations can be detected; and (2) monitoring the genomic profiles of TEX 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.