Objective To conduct a comparative study of the volume and location of the lumpectomy cavity delineated by metal clips and/or seroma on four-dimensional computed tomography (4DCT) for external-beam partial breast irradiation. Methods On 10 respiratory phases of 4DCT images with 15 breast cancer patients, gross tumor volumes (GTV_S) were delineated based on the metal clips at the boundaries of surgical cavity, seroma, and metal clips plus seroma to obtain GTV_C, GTV_S, and GTV_C+S, respectively. The volumes of GTV_C, GTV_S, and GTV_C+S were measured, and the conformity index (CI), degree of inclusion (DI), and centroid distance between each two GTV_S were calculated. One-way analysis of variance was used to compare volume and CI between GTV_C, GTV_S, and GTV_C+S;the paired t-test was used for comparison of DI;the Pearson correlation test was used to investigate the relationship of CI and DI with centroid distance. Results The volumes of GTV_C, GTV_S, and GTV_C+S were 23.15±13.34 cm³, 19.27±17.53 cm³, and 24.60±16.72 cm³, respectively (P=0.000). The CIs of GTV_C vs GTV_S, GTV_C vs GTV_C+S, and GTV_S vs GTV_C+S were 0.36±0.14, 0.60±0.14, and 0.53±0.20, respectively (P=0.000). The DI of GTV_S in GTV_C was significantly higher than that of GTV_C in GTV_S (0.67±0.21 vs 0.48±0.20, P=0.000);the DI of GTV_C in GTV_C+S was significantly higher than that of GTV_C+S in GTV_C (0.82±0.11 vs 0.71±0.19, P=0.000);the DI of GTV_S in GTV_C+S was significantly higher than that of GTV_C+S in GTV_S (0.91±0.14 vs 0.52±0.22;P=0.000). The DIs and CIs of GTV_C vs GTV_S, GTV_C vs GTV_C+S, and GTV_S vs GTV_C+Swere negatively correlated with their centroid distances (P=0.000 for all comparisons). Conclusions There are volume differences and spatial mismatches between the GTV_S delineated based on metal clips, seroma, and metal clips plus seroma.