In patients receiving breast radiotherapy, the risk of radiation pneumonitis has been associated with the volume of irradiated lung, and concomitant methotrexate, paclitaxel, and tamoxifen therapy. Many of the studies of radiation pneumonitis are based on estimates of pulmonary risk using central lung distance that is calculated using two-dimensional techniques. With the treatment of internal mammary nodes and three-dimensional treatment planning for breast cancer becoming increasingly more common, there is a need to further consider the impact of dose-volume metrics in assessing radiation pneumonitis risk. We herein present a case control study assessing the impact of clinical and dose-volume metrics on the development of radiation pneumonitis in patients receiving sequential chemotherapy and local-regional radiotherapy.