The epithelial cells of multicellular organisms form highly organized tissues specialized for the tasks of protection, secretion, and absorption, all of which require tight regulation of the core processes of cell polarity and tissue architecture. Disruption of these core processes is a critical feature of epithelial tumors. Cell polarity and tissue architecture are intimately linked, as proteins controlling cell shape are also responsible for proper localization and assembly of cell-cell junctions and three-dimensional tissue organization. The extracellular matrix underlying epithelial tissues supports tissue architecture and suppresses malignant growth through regulation of cell adhesion and activation of protective signaling cascades. Emerging evidence is uncovering the mechanisms by which polarity pathways alter the way epithelial cells organize and interact with the tissue microenvironment to promote aberrant growth and invasion during tumorigenesis. We discuss how cell polarity pathways regulate cell-cell junctions and highlight the new insights gained by investigating the role played by polarity pathways during the transformation of epithelial cells.