Accurate positioning of Radiation Therapy (RT) is critical to its safety and efficacy for postmastectomy patients. We measured the Planning Target Volume (PTV) margins using the daily Cone-Beam Computed Tomography (CBCT) for patients who received Modified Radical Mastectomies (MRMs). We analysed setup error data using CBCT for 58 postmastectomy patients, including 28 with left-sided breast cancers (15 patients who received single chest wall (CW) RT and 13 who received CW plus supraclavicular region (CW/SR) RT) and 30 with right-sided cancers (15 who received single CW RT and 15 who received CW/SR RT). The positional error was corrected and compared in x, y, and z translational planes for different breast cancer locations (left or right) and different target volumes (single CW or CW/SR). We analysed a total of 925 digital images using the On Board Imaging system (OBI). The Z translational errors in treating CW/SR were significantly greater than in treating CW alone for both left-sided (P=0.035) and right-sided (P=0.048) cancers. The Y translational errors were significantly greater for the left-sided cancers than for the right-sided cancers (P=0.001) for both CW alone (P=0.026) and CW/SR (P=0.001). The Z translational errors of CW/SR were significantly greater than of single CW, and the Y translational errors were significantly greater on the left side than on the right side. In treating postmastectomy patients with daily image-guided radiation therapy, positioning errors should be checked and corrected.