PURPOSE: This study was performed to evaluate the change in the lumpectomy cavity volumes before and after whole breast radiation therapy (WBRT) and to identify factors associated with the change of volume. MATERIALS AND METHODS: From September 2009 to April 2010, the computed tomography (CT) simulation data from 70 patients obtained before and after WBRT was evaluated. The lumpectomy cavity volumes were contoured based on surgical clips, seroma, and postoperative changes. Significant differences in the data from pre-WBRT CT and post-WBRT CT were assessed. Multiple variables were examined for correlation with volume reduction in the lumpectomy cavity. RESULTS: The mean and median volume reduction in the lumpectomy cavity after WBRT were 17.6 cm3 and 16.1 cm3, respectively with the statistical significance (p < 0.001). The volume reduction in the lumpectomy cavity was inversely correlated with time from surgery to radiation therapy (R = 0.390). The presence of seroma was significantly associated with a volumetric change in the lumpectomy cavity after WBRT (p = 0.011). CONCLUSION: The volume of lumpectomy cavity reduced significantly after WBRT. As the time from surgery to the start of WBRT increased, the volume reduction in the lumpectomy cavity during WBRT decreased. A strong correlation was observed between the presence of seroma and the reduced volume. To ensure appropriate coverage and to limit normal tissue exposure during boost irradiation in patients who has seroma at the time of starting WBRT, repeating CT simulation at boost planning is suggested.