BackgroundIn radiomic studies, several models are often trained with different combinations of feature selection methods and classifiers. The features of the best model are usually considered relevant to the problem, and they represent potential biomarkers. Features selected from statistically similarly performing models are generally not studied. To understand the degree to which the selected features of these statistically similar models differ, 14 publicly available datasets, 8 feature selection methods, and 8 classifiers were used in this retrospective study. For each combination of feature selection and classifier, a model was trained, and its performance was measured with AUC-ROC. The best-performing model was compared to other models using a DeLong test. Models that were statistically similar were compared in terms of their selected features.ResultsApproximately 57% of all models analyzed were statistically similar to the best-performing model. Feature selection methods were, in general, relatively unstable (0.58; range 0.35–0.84). The features selected by different models varied largely (0.19; range 0.02–0.42), although the selected features themselves were highly correlated (0.71; range 0.4–0.92).ConclusionsFeature relevance in radiomics strongly depends on the model used, and statistically similar models will generally identify different features as relevant. Considering features selected by a single model is misleading, and it is often not possible to directly determine whether such features are candidate biomarkers.