Although mammary glands are shared across all mammals, there is a variable incidence of mammary cancer across species. For example, humans and companion animals, such as cats and dogs, have a naturally high incidence of mammary cancer. This contrasts with animals with a low incidence of mammary cancer such as horses, cows, sheep, and pigs. While a lot of breast/mammary cancer research has been done using cancer models, our lab is focused on how normal mammary cells, from animals with variable incidences, respond to carcinogens. This represents an early stage of mammary cancer pathogenesis that could stratify the variable mammary cancer incidences seen across mammals. This work focuses on determining mechanisms that underlie the variable incidence using cats and horses as models representing an animal with a high and low incidence, respectively. Specifically, the work interrogates how microRNAs respond to carcinogens within mammary stem/progenitor cells in these two species. While the lab has historically used 2D mammary stem/progenitor cell cultures as a model, the work presented here lays out a method to generate 3D mammary organoids for virtually any mammal. These 3D mammary organoids more reliably recapitulate the tissue architecture and function of the mammary gland, making it a more physiologically relevant model to further investigate carcinogen responses across species. Finally, a scoping review protocol was generated to gather all the literature that uses or describes a 3D in vitro mammary culture model using a non-mouse/human animal, including veterinary and other nontraditional animals. This will provide an excellent repository of information for our lab and others who are interested in reviving the field of comparative mammary gland biology and cancer.