Feature extraction for radiomics studies typically comprises the following stages: Imaging, segmentation, image processing, and feature extraction. Each of these stages has associated uncertainties that can affect the quality of a radiomics model created using the resulting image features. For example, the imaging device manufacturer and model have been shown to impact the values of image features, as have pixel size and imaging protocol parameters. Image processing, such as low-pass filtering to reduce noise, also changes calculated image features and should be designed to optimize the information content of the resulting features. The details of certain feature algorithms, such as co-occurrence matrix bin sizes, are also important, and should be optimized for specific radiomics tasks. The volume of the region of interest should be considered as image features can be related to volume and can give unanticipated results when the volumes are too small. In this session we will describe approaches to quantify the variabilities in radiomics studies, including the most recent results quantifying these variabilities for CT, MRI and PET imaging. We will discuss methods to optimize image processing and feature extraction in order to maximize the information content of the image features. Finally, we will describe work to harmonize imaging protocols and feature calculations to help minimize uncertainties in radiomics studies. LEARNING OBJECTIVES At the end of this session, participants will be able to: 1. Identify the sources of uncertainty in radiomics studies (CT, PET, and MRI imaging) 2. Describe methods for quantifying the magnitude of uncertainties 3. Describe approaches for mitigating the effects of the uncertainties on radiomics models Funding from NIH, CPRIT, Varian, Elekta; L. Court, NCI, CPRIT, Varian, Elekta.