To compare localization of the lumpectomy cavity by using breast surface matching vs. clips for image-guided external beam accelerated partial breast irradiation. Twenty-seven patients with breast cancer with two computed tomography (CT) scans each had three CT registrations performed: (1) to bony anatomy, (2) to the center of mass (COM) of surgical clips, and (3) to the breast surface. The cavity COM was defined in both the initial and second CT scans after each type of registration, and distances between COMs (DeltaCOM(Bone), DeltaCOM(Clips), and DeltaCOM(Surface)) were determined. Smaller DeltaCOMs were interpreted as better localizations. Correlation coefficients were calculated for DeltaCOM vs. several variables. The DeltaCOM(Bone) (mean, 7 +/- 2 [SD] mm) increased with breast volume (r = 0.4; p = 0.02) and distance from the chest wall (r = 0.5; p = 0.003). Relative to bony registration, clip registration provided better localization (DeltaCOM(Clips) < DeltaCOM(Bone)) in 25 of 27 cases. Breast surface matching improved cavity localization (DeltaCOM(Surface) < DeltaCOM(Bone)) in 19 of 27 cases. Mean improvements (DeltaCOM(Bone) - DeltaCOM(Clips or Surface)) were 4 +/- 3 and 2 +/- 4 mm, respectively. In terms of percentage of improvement ([DeltaCOM(Bone) - DeltaCOM(Clips or Surface)]/DeltaCOM(Bone)), only surface matching showed a correlation with breast volume. Clip localization outperformed surface registration for cavities located superior to the breast COM. Use of either breast surface or surgical clips as surrogates for the cavity results in improved localization in most patients compared with bony registration and may allow smaller planning target volume margins for external beam accelerated partial breast irradiation. Compared with surface registration, clip registration may be less sensitive to anatomic characteristics and therefore more broadly applicable.