Tumor development and progression hinge upon ongoing co-evolution and crosstalk with the tumor microenvironment. In particular, fibroblasts in the stromal compartment are co-opted to support tumor growth and survival through heterotypic interactions with tumor cells. The cover depicts a novel co-culture method in which breast cancer organoids (white) are seeded alongside autologous cancer-associated fibroblasts (red). Using this new model, the authors demonstrate persistent tumor—stroma interactions that regulate the molecular phenotype and aggressiveness of cancer cells. For more information, see the Highlight on page 1613 and the article on page 1615.