An eight-year-old, male boxer dog was referred for the treatment of a large (5.5 x 5 cm), unresectable visceral mast cell tumour. The dog had a surgical resection performed one month before referral, and it had widespread metastases to the abdominal lymph nodes. The patient was treated with lomustine and prednisone and showed a rapid improvement and increased level of activity, weight gain and consistent tumour reduction. The patient remained in partial remission (defined as a greater than 50 per cent reduction in tumour volume) for seven months. Toxicity was acceptable and was limited to moderate anaemia and two episodes of neutropenia. At the completion of the seven months of therapy, the dog experienced a chemotherapy-induced sepsis, and the owners elected for euthanasia due to financial concerns. At that time, the tumour was still in partial remission. This case report suggests that a combination of lomustine and prednisone is an effective protocol for the palliation of aggressive visceral mast cell tumours.