Mouse models of colitis are used for efficacy testing of novel therapeutic compounds. A commonly used endpoint for colitis studies is the microscopic scoring of lesions on whole colon samples, either manually or by automated image analysis platforms. A comprehensive scoring system must evaluate the complete and continuous mucosal surface of the entire colon, so areas prone to show pathology are visible on a single hematoxylin and eosin (H&E)-stained slide. Slide preparation requires rolling the colon into a Swiss roll configuration in a biopsy cassette, fixing the tissue in formalin, embedding in paraffin, and sectioning sagittally through the center of the sample. Technical challenges often arise during the collection, embedding, and sectioning of samples, and errors lead to artifacts that compromise microscopic evaluation. Artifacts typically present as overlap of colon coils are termed ‘tissue folds’; segments of tissue absent from the slide is termed ‘tissue loss.’ We have identified key processing steps prone to contribute to these two artifacts and developed a method using the HistoPress embedding tool (American Master Tech) that significantly reduces their occurrence. [ABSTRACT FROM PUBLISHER]