Understanding precursors to distress and emotional well-being (EWB) experienced in anticipation of radiotherapy would facilitate the ability to intervene with this emotional upset (i.e. higher distress, lower EWB). Thus, this study tested an expectancy-based model for explaining emotional upset in breast cancer patients prior to radiotherapy. Women affected by breast cancer (N = 106) were recruited and participants completed questionnaires prior to commencing radiotherapy. Structural equation modelling was used to test a cross-sectional model, which assessed the ability of dispositional optimism (Life Orientation Test-Revised - two factors), response expectancies (Visual Analog Scale items), medical (type of surgery, cancer stage and chemotherapy history) and demographic (age, race, ethnicity, education and marital status) variables to predict both EWB (Functional Assessment of Chronic Illness Therapy - Emotional Well-being Subscale) and distress (Profile of Mood States - short version). The model represented a good fit to the data accounting for 65% of the variance in EWB and 69% in distress. Significant predictors of emotional upset were pessimism, response expectancies, Latina ethnicity, cancer stage and having had a mastectomy. These variables explained a large portion of emotional upset experienced prior to radiotherapy for breast cancer and are important to consider when aiming to reduce distress and improve EWB in this context.