Objectives To investigate the extent to which observer variability of CT lung nodule assessment may affect clinical treatment stratification in Wilms Tumor (WT) patients, according to the recent SIOP-RTSG UMBRELLA protocol. Methods I: CT thoraces of children with WT submitted for central review, were used to estimate size distribution of lung metastases. II: Scans were selected for blinded review by five radiologists to determine intra and inter-observer variability. They assessed identical scans on two occasions six months apart. III: Monte Carlo simulation (MCMC) was used to predict the clinical impact of observer variation when applying the UMBRELLA protocol size criteria. Results Lung nodules were found in 84 out of 360 (23%) children with WT. For 21 identified lung nodules, inter-observer limits of agreement (LOA) for the five readers were ±2.4mm and ±1.4mm (AP diameter), ±1.9mm and ±1.8mm (TS diameter) and ±2.0mm and ±2.4mm (LS diameter) at assessments 1 and 2. Intra-observer LOA across the three dimensions were ±1.5mm, ±2.2mm, ±3.5mm, ±3.1mm and ± 2.6mm (readers 1-5). MCMC demonstrated that 17% of the patients with a ‘true’ nodule size of 3mm will be scored as <3 mm, and 21% of the patients with a ‘true’ nodule size of <3mm will be scored as being 3 mm. Conclusion A significant intra-inter observer-variation was found when measuring lung nodules on CT for patients with WT. This may have significant implications on treatment stratification, and thereby outcome, when applying a threshold of 3 mm for a lung nodule to dictate metastatic status.