Canine transmissible venereal tumor (CTVT) is a transmissible cancer that affects the external genitalia of dogs. In this study, a female canine with CTVT in the vagina was treated with vincristine (0.75 mg/m2; intravenous (IV); weekly for eight cycles), the currently preferred drug for CTVT, but without any progress. Therefore, this case was considered resistant to vincristine, and the preferred alternative chemotherapy, doxorubicin, was suggested. However, based on echocardiographic evidence, the patient could not be administered doxorubicin. Thus, the administration of lomustine was proposed. Although there are no studies to support this decision, the authors based their decision on the fact that lomustine is effective for round cell tumors, and that CTVT belongs to this tumor group. After three doses (60 mg/m2; every 3 weeks) complete remission was achieved. The use of lomustine at a dose of 60 mg/m2 every 3 weeks for vincristine-resistant CTVT proved to be effective, without any harmful side effects. The treatment is cost-effective and simple to manage.