Developments in breast cancer therapies show potential for replacing simple and radical mastectomies with less invasive techniques. Localized thermal techniques encounter difficulties, preventing their widespread acceptance as replacements for surgical resection. Irreversible electroporation (IRE) is a non-thermal, minimally invasive focal ablation technique capable of killing tissue using electric pulses to create irrecoverable nano-scale pores in the cell membrane. Its unique mechanism of cell death exhibits benefits over thermal techniques including rapid lesion creation and resolution, preservation of the extracellular matrix and major vasculature, and reduced scarring. This study investigates applying IRE to treat primary breast tumors located within a fatty extracellular matrix despite IREs dependence on the heterogeneous properties of tissue. In vitro experiments were performed on MDA-MB-231 human mammary carcinoma cells to determine a baseline electric field threshold (1000 V/cm) to cause IRE for a given set of pulse parameters. The threshold was incorporated into a three-dimensional numerical model of a heterogeneous system to simulate IRE treatments. Treatment-relevant protocols were found to be capable of treating targeted tissue over a large range of heterogeneous properties without inducing significant thermal damage, making IRE a potential modality for successfully treating breast cancer. Information from this study may be used for the investigation of other heterogeneous tissue applications for IRE.