The electrochemical treatment (EChT) of cancerous tumors is a relatively noninvasive and efficient anti-tumor therapy. However, EChT has yet to receive widespread adoption-this is not only due to the lack of clinical trials demonstrating its efficacy, but also due to the lack of detailed three-dimensional models that consider more realistic tissue conditions. Thus, the preconditions for the widespread adoption of EChT are a thorough understanding of its underlying mechanisms of action and the ability to predict them. To this end, in this paper, we develop and describe comprehensive 2D mathematical models of the EChT process, encapsulating more realistic geometries and tissue conditions. Our analysis proceeds in two steps. First, we consider the surrounding tissue as a sodium chloride solution containing a bicarbonate buffer system. Next, we add another layer of complexity by integrating the buffer capacity of organic components to the previous bicarbonate buffer system to represent a more realistic tissue condition. The latter model also considers all the chlorination reactions that occur near the anode electrode. Finally, we separately investigate the effects of applied current on the temperature profile inside the tissue during electrolysis. The results show that tumor necrosis scales non-linearly as a function of the Coulomb dosage. Parametric studies confirmed that in very low current densities applied at the electrodes, chlorine reactions are an important source of H+ ion generation, but at higher current densities, it is mainly the electrolysis that contributes to lesion size. In summary, should the model be further developed to consider more realistic tissue conditions in 3D, it can be used by practitioners to predict the effects of various factors in the EChT process in advance of treatment. Published by Elsevier Ltd.