The mammary gland consists of epithelial and stromal cells that communicate through the extracellular matrix (ECM). Disruption of this communication can lead to breast cancer. During development, the mammary gland exhibits properties similar to cancer, and many factors involved in development also play roles in cancer. Stromal factors are crucial for mammary development and tumorigenesis. The mammary gland branches through two mechanisms: TEB bifurcation and side branching. TEBs are rapidly proliferating cells that invade stromal tissue, similar to solid tumors. Proper branching requires the ECM and surrounding microenvironment. Factors like MMPs, Wnts, and gelsolin are involved in side branching and can contribute to tumorigenesis. TGFβ is a key factor in preventing inappropriate branching and is also involved in tumorigenesis. The stroma provides signals that regulate epithelial-stromal crosstalk, including factors like PTHrP, IGF-I, and others. Inflammatory cells, such as macrophages and eosinophils, play important roles in mammary development and tumor progression. Stromal regulation of involution involves apoptosis and adipogenesis. The mammary gland undergoes three stages of involution, each regulated by distinct mechanisms. Stromal factors like TGFβ, MMPs, and TIMP-3 regulate apoptosis and involution. The stromal environment is crucial for mammary development and cancer progression. Understanding the interactions between epithelial and stromal cells is essential for developing treatments for breast cancer and other diseases. Future research should focus on the molecular mechanisms underlying epithelial-stromal crosstalk and how these interactions contribute to cancer development and progression.The mammary gland consists of epithelial and stromal cells that communicate through the extracellular matrix (ECM). Disruption of this communication can lead to breast cancer. During development, the mammary gland exhibits properties similar to cancer, and many factors involved in development also play roles in cancer. Stromal factors are crucial for mammary development and tumorigenesis. The mammary gland branches through two mechanisms: TEB bifurcation and side branching. TEBs are rapidly proliferating cells that invade stromal tissue, similar to solid tumors. Proper branching requires the ECM and surrounding microenvironment. Factors like MMPs, Wnts, and gelsolin are involved in side branching and can contribute to tumorigenesis. TGFβ is a key factor in preventing inappropriate branching and is also involved in tumorigenesis. The stroma provides signals that regulate epithelial-stromal crosstalk, including factors like PTHrP, IGF-I, and others. Inflammatory cells, such as macrophages and eosinophils, play important roles in mammary development and tumor progression. Stromal regulation of involution involves apoptosis and adipogenesis. The mammary gland undergoes three stages of involution, each regulated by distinct mechanisms. Stromal factors like TGFβ, MMPs, and TIMP-3 regulate apoptosis and involution. The stromal environment is crucial for mammary development and cancer progression. Understanding the interactions between epithelial and stromal cells is essential for developing treatments for breast cancer and other diseases. Future research should focus on the molecular mechanisms underlying epithelial-stromal crosstalk and how these interactions contribute to cancer development and progression.