Dogs have a similar incidence of spontaneous cancers as people, and a noninvasive test to monitor disease status in dogs would be of great value. Humans with cancer often have increased levels of cell-free circulating DNA in their plasma, which has shown promise for diagnosis, prognosis and detection of residual disease. We hypothesized that dogs with cancer have increased circulating DNA compared with healthy dogs or dogs with non-neoplastic diseases. Plasma DNA was measured in 40 healthy dogs, 20 dogs with non-neoplastic diseases and 80 dogs with cancer. The reference interval for plasma DNA in healthy dogs was 1-15 ng mL(-1). Dogs with lymphoma and lymphoid leukaemia had significantly higher concentrations (range: 0-91 ng mL(-1), P < 0.0001). Antigen receptor rearrangement assays suggest that plasma DNA had the same clonality as the primary lymphoid tumours. Dogs with lymphoid neoplasia and plasma DNA >25 ng mL(-1) had shorter remission times than those with < 25 ng mL(-1) (P = 0.0116). In contrast to humans, where increased plasma DNA is seen in many diseases, dogs with nonlymphoid malignancies and non-neoplastic diseases had plasma DNA concentrations similar to healthy dogs. This study shows that a portion of dogs with lymphoid neoplasia have increased tumour-derived plasma DNA, which serves as a negative prognostic indicator.