One of the main questions put forth by NASA and the European Space Agency (ESA) is whether or not an organism, especially mankind, can complete an entire life cycle in space. With this in mind, it is essential to study the effect of spaceflight on reproductive tissues. Using simulated microgravity techniques and whole-body radiation we sought to determine if females subjected to a simulated spaceflight environment have increased incidences of uterine cancer. Uterine tissue from mice subjected to simulated spaceflight was analyzed using immunohistochemical staining and western blot analysis. Two pathways commonly activated in cancer were investigated. Additionally, the uterine tissue was evaluated for gross morphological changes using standard histological staining. The findings of this study indicate that none of the treatment parameters used to simulate the spaceflight environment were found to induce uterine cancer.