The interactions between breast epithelium and stroma are fundamental to normal tissue homeostasis and for tumor initiation and progression. Gene expression studies of in vitro coculture models demonstrate that in vitro models have relevance for tumor progression in vivo. For example, stromal gene expression has been shown to vary in association with tumor subtype in vivo, and analogous in vitro cocultures recapitulate subtype-specific biological interactions. Cocultures can be used to study cancer cell interactions with specific stromal components (e.g., immune cells, fibroblasts, endothelium) and different representative cell lines (e.g., cancer-associated versus normal-associated fibroblasts versus established, immortalized fibroblasts) can help elucidate the role of stromal variation in tumor phenotypes. Gene expression data can also be combined with cell-based assays to identify cellular phenotypes associated with gene expression changes. Coculture systems are manipulable systems that can yield important insights about cell-cell interactions and the cellular phenotypes that occur as tumor and stroma co-evolve.