Chemokines have been recently recognized as important regulators of breast malignancy; however, much remains unknown regarding their roles in this disease. Improved understanding of chemokine contribution to breast cancer often requires studies in which the expression levels of chemokines by the tumor cells are modified (increased or decreased). In addition, it is essential to determine the roles of various chemokines in experimental in vivo model systems of breast cancer, using hormone-dependent or -independent human breast tumor cells (such as MCF-7, T47D and MDA-MB-231 cells). Since investigators often encounter difficulties in implementing these techniques in their studies of breast cancer, we hereby provide a detailed description of microporation approaches for modifying chemokine expression levels in human breast tumor cells, and of the measures required for establishment of xenograft models of primary tumors and of metastasis by such cells. In the breast malignancy context, the guidelines presented herein should enable researchers in the field to establish essential means for determination of chemokine roles in this disease.