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Background: Targeted osmotic lysis (TOL) is a novel technology that involves concomitant stimulation of voltage-gated sodium channels (VGSCs) and the pharmacological blockade of Na + , K + -ATPase causing lysis of highly malignant cancer cells. Hypothesis/Objectives . TOL offers an option for treating advanced carcinomas in companion animals. Animals . Two cats and 2 dogs that presented to veterinary hospitals for evaluation and treatment of one of several forms of carcinoma., Methods: Digoxin was administered to achieve steady-state, therapeutic concentrations. The animals were then exposed to pulsed electric field stimulation. Pre- and posttreatment assessments of tumor size and quality of life were compared. The treatment frequency and survivability varied, based on the patient's premorbid functioning and response to treatment., Results: Regardless of cancer type, TOL consistently increased survival beyond expected, often improving, but without compromising of quality of life. Conclusions and Clinical Importance . TOL warrants consideration as an option for managing advanced carcinomas., Competing Interests: H.J.G., P.R.M, and D.P. are cofounders and managing members of Oleander Medical Technologies, L.LC., (Copyright © 2022 Harry J. Gould III et al.)