Spaceflight exposes astronauts to a host of environmental factors which could increase their risk for cancer. Epidemiological studies have shown an increased incidence of breast cancer in female commercial flight attendants, with occupational risk factors as one of the proposed mechanisms for the higher incidence in this cohort. Since female astronauts are exposed to similar occupational conditions as flight attendants, they too may be at an increased risk for breast cancer. With the planning of exploration class missions to the Moon and to Mars it is important to assess and minimize the risk for breast malignancy, and to have a well-defined protocol for the diagnosis and treatment of a breast mass discovered during a mission. Risk factors for development of breast cancer in the female astronaut include ionizing radiation, disrupted melatonin homeostasis secondary to circadian shifting, chemical exposure, and changes in immune function. Preflight, in-flight, and postflight screening and management modalities include imaging and fine needle aspiration (FNA). Employing such a strategy may provide a viable management approach in the case of a newly diagnosed breast mass inflight.