INTRODUCTION: With the purpose of implementing gated radiotherapy for lung cancer patients, this study investigated the interfraction variations in tumour size and internal displacement over entire treatment courses. To explore the potential of image guided radiotherapy (IGRT) the variations were measured using a set-up strategy based on imaging of bony landmarks and compared to a strategy using in room lasers, skin tattoos and cupper landmarks. MATERIALS AND METHODS: During their six week treatment course of 60Gy in 2Gy fractions, ten patients underwent 3 respiratory gated CT scans. The tumours were contoured on each CT scan to evaluate the variations in volumes and position. The lung tumours and the mediastinal tumours were contoured separately. The positional variations were measured as 3D mobility vectors and correlated to matching of the scans using the two different strategies. RESULTS: The tumour size was significantly reduced from the first to the last CT scan. For the lung tumours the reduction was 19%, p=0.03, and for the mediastinal tumours the reduction was 34%, p=0.0007. The mean 3D mobility vector and the SD for the lung tumours was 0.51 cm (+/-0.21) for matching using bony landmarks and 0.85 cm (+/-0.54) for matching using skin tattoos. For the mediastinal tumours the corresponding vectors and SD's were 0.55 cm (+/-0.19) and 0.72 cm (+/-0.43). The differences between the vectors were significant for the lung tumours p=0.004. The interfractional overlap of lung tumours was 80-87% when matched using bony landmarks and 70-76% when matched using skin tattoos. The overlap of the mediastinal tumours were 60-65% and 41-47%, respectively. CONCLUSIONS: Despite the use of gating the tumours varied considerably, regarding both position and volume. The variations in position were dependent on the set-up strategy. Set-up using IGRT was superior to set-up using skin tattoos.