To study the geometric uncertainties in the treatment and evaluate the adequacy of the margins employed for planning target volume (PTV) generation in the treatment of focal conformal radiotherapy (CRT) for patients with brain tumors treated with different head support systems. The study population included 11 patients with brain tumors who were to be treated with CRT. Contrast-enhanced planning CT scan (5-mm spacing and reconstructed to 2 mm) of brain were performed. Five patients were immobilized using neck support only (NR-only) and six patients had neck support with flexion (NRF), the form of immobilization being decided by the likely beam arrangements to be employed for that particular patient. The data was transferred to the planning system (CadPlan) where three-dimensional conformal radiation therapy was planned. Digitally reconstructed radiographs (DRRs) were created for the orthogonal portals with the fixed field sizes of 10 x 10 taken at the isocenter. Treatment verification was done using an amorphous silicon detector portal imaging device for using orthogonal portals and the DRR was used as a reference image. An image matching software was used to match the anatomical landmarks in the DRR and the portal imaging and the displacement of the portals in x, y axis and rotation were noted in the anteroposterior (AP) and lateral images. Electronic portal imaging was repeated twice weekly and an average of 8-14 images per patient was recorded. The mean deviation in all the directions was calculated for the each patient. Comparison of setup errors between the two head support systems was done. A total 224 images were studied in anterior and lateral portals. The patient group with NR-only had 100 images, while the NRF group had 124 images. The mean total error in all patients, NR-only group, and NRF group was 0.33 mm, 0.24 mm, and 0.79 mm in the mediolateral (ML) direction; 1.16 mm, 0.14 mm, and 2.22 mm in the AP direction; and 0.67 mm, 0.31 mm, and 0.96 mm in the superoinferior (SI) direction, respectively. The systematic error (S) in all patients, NR-only group, and NRF group in the ML direction was 0.31 mm, 0.28 mm, and 0.78 mm; 1.29 mm, 0.1 mm, and 2.24 mm in the AP direction; and 0.75 mm, 0.52 mm, and 0.94 mm in the SI direction, respectively. Random error (s) in all patients, NR-only group, and NRF group in the ML direction was 1.25 mm, 1.04 mm, and 1.41 mm; 1.31 mm, 1.36 mm, and 1.28 mm in the AP direction; 1.38 mm, 1.37 mm, and 1.39 mm in the SI direction, respectively. In all patients, the PTV margin with Stroom's formula in the NR-only and NRF group was 1.29 mm and 2.55 mm in the ML, 1.15 mm and 5.38 mm in the AP, and 2.0 mm and 2.85 mm in the SI directions, respectively. A PTV margin of 5 mm appears to be adequate; further reduction to 3 mm may be considered based on our results. Errors were significantly higher in the AP direction with NRF when compared to NR-only. Differential PTV margin may therefore be considered, with more margin in the AP and less in other directions, especially with the use of flexion devices.