Abstract Deep learning is often used for automated diagnosis support in biomedical image processing scenarios. Annotated datasets are essential for the supervised training of deep neural networks. The problem of consistent and noise-free annotation remains for experts such as pathologists. The variability within an annotator (intra) and the variability between annotators (inter) are current challenges. In clinical practice or biology, instance segmentation is a common task, but a comprehensive and quantitative study regarding the impact of noisy annotations lacks. In this paper, we present a concept to categorize and simulate various types of annotation noise as well as an evaluation of the impact on deep learning pipelines. Thereby, we use the multi-organ histology image dataset MoNuSeg to discuss the influence of annotator variability. We provide annotation recommendations for clinicians to achieve high-quality automated diagnostic algorithms.