A method is described for generating a prediction of a disease classification error for a magnified, digital microscope slide image of a tissue sample. The image is composed of a multitude of patches or tiles of pixel image data. An out-of-focus degree per patch is computed using a machine learning out-of-focus classifier. Data representing expected disease classifier error statistics of a machine learning disease classifier for a plurality of out-of-focus degrees is retrieved. A mapping of the expected disease classifier error statistics to each of the patches of the digital microscope slide image based on the computed out-of-focus degree per patch is computed, thereby generating a disease classifier error prediction for each of the patches. The disease classifier error predictions thus generated are aggregated over all of the patches.