BACKGROUND Radiotherapy based on MRI only (MRI-only RT) shows a promising potential for the brain. Much research focuses on creating a pseudo computed tomography (pCT) from MRI for treatment planning while little attention is often paid to the treatment delivery. Here, we investigate if cone beam CT (CBCT) can be used for MRI-only image-guided radiotherapy (IGRT) and for verifying the correctness of the corresponding pCT. MATERIAL AND METHODS Six patients receiving palliative cranial RT were included in the study. Each patient had three-dimensional (3D) T1W MRI, a CBCT and a CT for reference. Further, a pCT was generated using a patch-based approach. MRI, pCT and CT were placed in the same frame of reference, matched to CBCT and the differences noted. Paired pCT-CT and pCT-CBCT data were created in bins of 10 HU and the absolute difference calculated. The data were converted to relative electron densities (RED) using the CT or a CBCT calibration curve. The latter was either based on a CBCT phantom (phan) or a paired CT-CBCT population (pop) of the five other patients. RESULTS Non-significant (NS) differences in the pooled CT-CBCT, MRI-CBCT and pCT-CBCT transformations were noted. The largest deviations from the CT-CBCT reference were < 1 mm and 1°. The average median absolute error (MeAE) in HU was 184 ± 34 and 299 ± 34 on average for pCT-CT and pCT-CBCT, respectively, and was significantly different (p < 0.01) in each patient. The average MeAE in RED was 0.108 ± 0.025, 0.104 ± 0.011 and 0.099 ± 0.017 for pCT-CT, pCT-CBCT phan (p < 0.01 on 2 patients) and pCT-CBCT pop (NS), respectively. CONCLUSIONS CBCT can be used for patient setup with either MRI or pCT as reference. The correctness of pCT can be verified from CBCT using a population-based calibration curve in the treatment geometry.