Background and objectiveThe tissue morphology of the intestinal surface is architecturally complex with finger-like projections called villi, and glandular structures called crypts. The ratio of villus height-to-crypt depth ratio (Vh:Cd) is used to quantitatively assess disease severity and response to therapy for intestinal enteropathies, such as celiac disease and is currently quantified manually. Given the time required, manual Vh:Cd measurements have largely been limited to clinical trials and are not used widely in clinical practice. We developed ViCE (Villus Crypt Evaluator), a user-friendly software that automatically quantifies histological parameters in standard hematoxylin and eosin-stained intestinal biopsies. MethodsViCE is based on mathematical morphology operations and is scale and staining agnostic. It evaluates tissue orientation, identifies geometrical structure, and outputs key tissue measurements. ResultsThe output measurements of Vh:Cd are concordant with manual quantifications across multiple datasets. ConclusionsThe underlying mathematical morphological approach for ViCE is robust, and reproducible and easily adaptable for measurement of morphological features in other tissues.