Cell migration and metastasis are key features of aggressive tumors. These processes can be difficult to study, as they often occur deep within the body of a cancer patient or an experimental animal. In vitro assays are able to model some aspects of these processes, and a number of assays have been developed to assess cancer cell motility, migration, and invasion. However, in vitro assays have inherent limitations that may miss important aspects of these processes as they occur in vivo. The chick embryo provides a powerful model for studying these processes in vivo, facilitated by the external and accessible nature of the chorioallantoic membrane (CAM), a well-vascularized tissue that surrounds the embryo. When coupled with multiple fluorescent approaches to labeling both cancer cells and the embryonic vasculature, along with image analysis tools, the chick CAM model offers cost-effective, rapid assays for studying cancer cell migration and metastasis in a physiologically-relevant, in vivo setting. Here, we present recent developments of detailed procedures for using shell-less chick embryos, coupled with fluorescent labeling of cancer cells and/or chick vasculature, to study cancer cell migration and metastasis in vivo.