Purpose To determine whether T2-weighted MRI improves seroma cavity (SC) and whole breast (WB) interobserver conformity for radiation therapy purposes, compared with the gold standard of CT, both in the prone and supine positions. Methods and Materials Eleven observers (2 radiologists and 9 radiation oncologists) delineated SC and WB clinical target volumes (CTVs) on T2-weighted MRI and CT supine and prone scans (4 scans per patient) for 33 patient datasets. Individual observer's volumes were compared using the Dice similarity coefficient, volume overlap index, center of mass shift, and Hausdorff distances. An average cavity visualization score was also determined. Results Imaging modality did not affect interobserver variation for WB CTVs. Prone WB CTVs were larger in volume and more conformal than supine CTVs (on both MRI and CT). Seroma cavity volumes were larger on CT than on MRI. Seroma cavity volumes proved to be comparable in interobserver conformity in both modalities (volume overlap index of 0.57 (95% Confidence Interval (CI) 0.54-0.60) for CT supine and 0.52 (95% CI 0.48-0.56) for MRI supine, 0.56 (95% CI 0.53-0.59) for CT prone and 0.55 (95% CI 0.51-0.59) for MRI prone); however, after registering modalities together the intermodality variation (Dice similarity coefficient of 0.41 (95% CI 0.36-0.46) for supine and 0.38 (0.34-0.42) for prone) was larger than the interobserver variability for SC, despite the location typically remaining constant. Conclusions Magnetic resonance imaging interobserver variation was comparable to CT for the WB CTV and SC delineation, in both prone and supine positions. Although the cavity visualization score and interobserver concordance was not significantly higher for MRI than for CT, the SCs were smaller on MRI, potentially owing to clearer SC definition, especially on T2-weighted MR images.