Computational pathology can significantly benefit from ontologies to standardize the employed nomenclature and help with knowledge extraction processes for high-quality annotated image datasets. The end goal is to reach a shared model for digital pathology to overcome data variability and integration problems. Indeed, data annotation in such a specific domain is still an unsolved challenge and datasets cannot be steadily reused in diverse contexts due to heterogeneity issues of the adopted labels, multilingualism, and different clinical practices. Material and methods : This paper presents the ExaMode ontology, modeling the histopathology process by considering 3 key cancer diseases (colon, cervical, and lung tumors) and celiac disease. The ExaMode ontology has been designed bottom-up in an iterative fashion with continuous feedback and validation from pathologists and clinicians. The ontology is organized into 5 semantic areas that defines an ontological template to model any disease of interest in histopathology. Results :The ExaMode ontology is currently being used as a common semantic layer in: (i) an entity linking tool for the automatic annotation of medical records; (ii) a web-based collaborative annotation tool for histopathology text reports; and (iii) a software platform for building holistic solutions integrating multimodal histopathology data. Discussion : The ontology ExaMode is a key means to store data in a graph database according to the RDF data model. The creation of an RDF dataset can help develop more accurate algorithms for image analysis, especially in the field of digital pathology. This approach allows for seamless data integration and a unified query access point, from which we can extract relevant clinical insights about the considered diseases using SPARQL queries.