With portal imaging devices we can easily determine the position of bones in the patient, but we cannot visualize soft tissues. Kilo voltage cone beam computed tomography (CBCT) imaging integrated to treatment machine is relatively a new technique and provides higher resolution of soft tissues for imaging. In this study, our aim was to measure the differences between 2D-2D and 3D-3D registration based set-ups. We investigated whether using kV cone beam CT reduced setup errors compared to kV portal imaging. Four patients with the diagnosis of head and neck cancer (2 patients with cancer in the base of tongue, 2 with hypopharyngeal cancer) and 6 patients with prostate cancer were included in our study. The treatments were delivered with IMRT. kvCBCT-kv film comparisions were evaluated in 44 sets of data for head and neck cancer patients, and in 130 sets of data for prostate cancer patients. We analyzed the necessary planning target volume (PTV) margins for each group when only kv portal imaging is performed every day and found that a margin of 2.1 and 1.5 mm in all directions would be sufficient in case of pelvic tumors and head and neck cancers respectively if the lw portal images are performed every day. Compared to the literature the shifts were minimal when kvCBCT was performed after lw portal imaging. The immobilization procedures, followed strictly, may be reason for this observation.