【Aims】 Many studies of human subjects have demonstrated the utility of assessing serum levels of endothelin-1 (ET-1) and big ET-1 as clinical biomarkers in cardiopulmonary and neoplastic diseases. In this study we explored the feasibility of using serum big ET-1 as a reliable veterinary marker in dogs with various cardiopulmonary and neoplastic diseases. 【Main methods】 Serum big ET-1 levels were measured by ELISA in dogs with cardiopulmonary (n = 21) and neoplastic diseases (n = 57). Dogs exhibiting cardiopulmonary disease were divided into two groups based on the velocity of tricuspid valve regurgitation (3.0 > m/s) measured by ultrasound: without and with pulmonary hypertension. Big ET-1 levels for the dogs with the diseases were compared with levels in normal healthy dogs (n = 17). 【Key findings】 Dogs with cardiopulmonary disease (4.6 ± 4.6 pmol/l) showed a significantly (P < 0.01) higher level of big ET-1 than healthy control dogs (1.1 ± 0.53 pmol/l). Serum levels in the dogs with pulmonary hypertension (6.2 ± 5.3 pmol/l) were significantly (P < 0.01) higher than those without pulmonary hypertension (2.0 ± 0.6 pmol/l). Dogs with hemangiosarcoma (5.6 ± 2.2 pmol/l), adenocarcinoma (2.0 ± 1.8 pmol/l), histiocytic sarcoma (3.3 ± 1.9 pmol/l), chondrosarcoma or osteosarcoma (3.0 ± 1.6 pmol/l) and hepatocellular carcinoma (2.7 ± 1.8 pmol/l) showed significantly (P < 0.05) higher levels than healthy control dogs. 【Significance】These findings point to the potential of serum big ET-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs.