Cancer progression-the evolution of malignant tumors towards metastatic dissemination-is a complex, multistep process orchestrated by neoplastic cells but aided by elements of the tumor microenvironment such as macrophages, activated fibroblasts, and endothelial cells. During tumor progression, cancer cells acquire a number of traits, such as the ability to undergo unrestrained proliferation, to resist pro-apoptotic insults, and to invade through tissue boundaries. Genetic and epigenetic changes conspire to drive the emergence of these traits against the backdrop of host selection. It is becoming increasingly clear that certain integrins and integrin-signaling components amplify oncogenic signaling to promote tumor progression. Mouse models of cancer provide useful, if not necessary, experimental systems to study tumor initiation and progression in vivo and to test novel therapeutic approaches. We have utilized mouse models of mammary tumorigenesis to examine the role of integrin α6β4 signaling in tumor progression in vivo. In this chapter, we describe a collection of cell biological and genetic methods that may aid in characterizing the roles of integrin signals in mammary tumorigenesis.