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Electrochemotherapy is a combination of high electric field and anticancer drugs. The treatment basis is electroporation or electropermeabilization of the cell membrane. Electroporation is a threshold phenomenon and, for efficient treatment, an adequate local distribution of electric field within the treated tissue is important. When this local electric field is not enough, there is a regrown tumor cell; however, if it is stronger than necessary, permanent damage to the tissue occurs. In the treatment of dogs, electrochemotherapy is not yet an established treatment for mast cell tumor in veterinary medicine, although there are studies showing evidence of its effectiveness. In this study, we examined electrochemotherapy of dog mast cell tumor with numerical simulation of local electric field distribution. The experimental result was used to validate the numerical models. The effect of tumor position and tissue thickness (tumor in different parts of dog body) was investigated using plate electrodes. Our results demonstrated that the electrochemotherapy is efficient and flexible, and even when the tumor extends into the subcutis, the treatment with plate electrode eliminated the tumor cells. This result suggests that electrochemotherapy is a suitable method to treat mast cell tumors in dog., (Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)