Background: It is vital to precisely evaluate the setup errors to ensure quality assurance in the subjects undergoing radiation therapy for various cancers. Aim: The present cross-sectional clinical study was aimed to assess the random, systematic, PTV (planning target volume) margin errors in subjects with breast, head, and neck cancer. Methods: The study assessed 100 subjects with breast cancer and 96 subjects with head and neck cancer. EPIDs (electronic portal imaging) were used to perform the treatment setup followed by the irradiation. The Herk formula was used to assess the errors in the treatment and the results were formulated. Results: The PTV margin shifting error was 1.41, 2.31, and 1.48 mm for breast cancer and was 2.77, 1.53, and 4.36 mm for head and neck cancer on the x, y, and z-axis respectively. The random error was 0.64, 0.70, and 0.77 mm for breast cancer and 0.80, 0.66, and 0.92 mm for head and neck cancer. However, the systematic error was 0.37, 0.72, and 0.36 mm for breast cancer and 0.87, 0.41, and 1.47 mm for head and neck cancer on the x, y, and z-axis respectively. Conclusion: The study, within its limitations, concludes that setup errors change in cancer depending on the location of the tumors. The present study points to the potential advantages of using electronic portal imaging devices to reduce the uncertainties for the procedures of setup verifications.