The authors explore the feasibility of using whole-genome sequencing to detect chromosomal alterations in tumour DNA that is found in the circulating blood of cancer patients. Leary et al. show that detecting structural alterations can clearly distinguish samples from patients with colorectal cancer or breast cancer from controls, making this a promising avenue for non-invasive diagnosis. However, the sensitivity of the method depends on the amount of DNA in the circulation, and the cost of sequencing would need to be further reduced for such an approach to be implemented.