The tumor microenvironment (TME) harbors cancer-associated fibroblasts (CAF) and other factors that promote tumor growth and progression. Modeling the TME is challenging given mouse models lack human CAF and extracellular matrix (ECM) components, and two-dimensional cell cultures fail to recapitulate integral in vivo structures. Addressing these challenges could facilitate studies capable of discovering novel TME-tumor interactions and therapeutic targets therein. In their study, Singh and colleagues devised a three-dimensional organotypic model, containing human triple-negative breast cancer (TNBC) cells, CAF, and an extracellular collagen matrix in an effort to study TME-TNBC interactions. The cover depicts a confocal image of the three-dimensional model. TNBC cells (green) form a mass embedded in a collagen matrix (cyan) containing dispersed CAF (red), reproducing spatial organization of native breast tumors. The authors utilized the model to demonstrate that CAF promote TNBC ECM invasion through a specific HGF-cMET signaling mechanism. This phenomenon is visible as green TNBC cell dissemination from the mass into the cyan collagen matrix in the cover image.