BACKGROUND Recent evidence suggests that women who receive treatment for breast cancer may experience multiple symptoms that decrease their functional status and quality of life. Few studies evaluated the occurrence, severity, and distress of multiple symptoms in women at the initiation of radiation therapy (RT) for breast cancer. OBJECTIVE This study evaluated for differences in symptoms occurrence, severity, and distress between women with breast cancer who did and did not receive chemotherapy (CTX) prior to RT. METHODS Prior to the initiation of RT, patients completed the Memorial Symptom Assessment Scale (MSAS) that evaluated multiple dimensions of 32 symptoms. Differences in occurrence, severity, and distress scores between the 2 CTX groups were evaluated using χ and Mann-Whitney U tests. RESULTS The 5 symptoms with the highest occurrence rates were lack of energy, worrying, difficulty sleeping, feeling drowsy, sweats, and pain. Women who received CTX prior to RT experienced twice as many symptoms as women who did not receive CTX. Except from difficulty sleeping, the 5 most prevalent symptoms were not the most severe or distressing. A poorer functional status, a higher comorbidity score, and previous CTX were all predictors of a higher number of symptoms. CONCLUSIONS Women with breast cancer experience large numbers of symptoms at the initiation of RT. Previous CTX doubles the number of symptoms that women report. IMPLICATIONS FOR PRACTICE Findings suggest that clinicians need to use a multidimensional symptom assessment tool in women with breast cancer at the initiation of RT.