Background: The purpose of this study was to evaluate the impact of Cone Beam CT (CBCT) based setup correction on total dose distributions in fractionated frameless stereotactic radiation therapy of intracranial lesions. Methods: Ten patients with intracranial lesions treated with 30 Gy in 6 fractions were included in this study. Treatment planning was performed with Oncentra(R) for a SynergyS(R) (Elekta Ltd, Crawley, UK) linear accelerator with XVI(R) Cone Beam CT, and HexaPOD (TM) couch top. Patients were immobilized by thermoplastic masks (BrainLab, Reuther). After initial patient setup with respect to lasers, a CBCT study was acquired and registered to the planning CT (PL-CT) study. Patient positioning was corrected according to the correction values (translational, rotational) calculated by the XVI(R) system. Afterwards a second CBCT study was acquired and registered to the PL-CT to confirm the accuracy of the corrections. An in-house developed software was used for rigid transformation of the PL-CT to the CBCT geometry, and dose calculations for each fraction were performed on the transformed CT. The total dose distribution was achieved by back-transformation and summation of the dose distributions of each fraction. Dose distributions based on PL-CT, CBCT (laser set-up), and final CBCT were compared to assess the influence of setup inaccuracies. Results: The mean displacement vector, calculated over all treatments, was reduced from (4.3 +/- 1.3) mm for laser based setup to (0.5 +/- 0.2) mm if CBCT corrections were applied. The mean rotational errors around the medial-lateral, superior-inferior, anterior-posterior axis were reduced from (-0.1 +/- 1.4)degrees, (0.1 +/- 1.2)degrees and (-0.2 +/- 1.0)degrees, to (0.04 +/- 0.4)degrees, (0.01 +/- 0.4)degrees and (0.02 +/- 0.3)degrees. As a consequence the mean deviation between planned and delivered dose in the planning target volume (PTV) could be reduced from 12.3% to 0.4% for D-95 and from 5.9% to 0.1% for D-av. Maximum deviation was reduced from 31.8% to 0.8% for D-95, and from 20.4% to 0.1% for D-av. Conclusion: Real dose distributions differ substantially from planned dose distributions, if setup is performed according to lasers only. Thermoplasic masks combined with a daily CBCT enabled a sufficient accuracy in dose distribution.