The reliability of radiomics features (RFs) is crucial for quantifying tumour heterogeneity. We assessed the influence of imaging, segmentation, and processing conditions (quantization range, bin number, signal-to-noise ratio [SNR], and unintended outliers) on RF measurement. Low SNR and unintended outliers increased the standard deviation and mean values of histograms to calculate the first-order RFs. Variations in imaging processing conditions significantly altered the shape of the probability distribution (centre of distribution, extent of dispersion, and segmentation of probability clusters) in second-order RF matrices (i.e. grey-level co-occurrence and grey-level run length), thereby eventually causing fluctuations in RF estimation. Inconsistent imaging and processing conditions decreased the number of reliably measured RFs in terms of individual RF values (intraclass correlation coefficient ≥0.75) and inter-lesion RF ratios (coefficient of variation <15%). No RF could be reliably estimated under inconsistent SNR and inclusion of outlier conditions. By contrast, with high SNR and no outliers, all first-order RFs, 11 (42%) grey-level co-occurrence RFs and five (42%) grey-level run length RFs showed acceptable reliability. Our study suggests that optimization of SNR, exclusion of outliers, and application of relevant quantization range and bin number should be performed to ensure the robustness of radiomics studies assessing tumor heterogeneity.