An exciting frontier in biology is understanding the functions of basic cell biological machinery in complex tissues. This approach is expected to uncover novel modes of regulation as well as reveal how core machinery is repurposed by different tissues to accomplish different physiological outputs. F-actin plays roles in cell shape, adhesion, migration and signaling – diverse functions that require a specific organization established by a myriad of regulators. Here, we discuss the role of the actin nucleating Arp2/3 complex and the unexpected roles that it plays in a stratified epithelial tissue, the epidermis. While many expected phenotypes such as defects in architecture and cell adhesion were lacking, loss of the Arp2/3 complex activity resulted in epidermal barrier and differentiation defects. This teaches us that, while informative, cell culture approaches are limiting and that studies of the Arp2/3 complex in diverse tissues are expected to yield many more surprises.