A clinically-oriented foundation model for intraoperative pathology

Abstract Intraoperative pathology is pivotal to precision surgery, yet its clinical impact is constrained by diagnostic complexity and the limited availability of high-quality frozen-section data. While computational pathology has made significant strides, the lack of large-scale, prospective validation has impeded its routine adoption in surgical workflows. Here, we introduce CRISP, a clinically oriented foundation model developed on over 100,000 frozen sections from ten medical centers, specifically designed to provide Clinically-oriented Robust Intraoperative Support for Pathology (CRISP). CRISP was comprehensively evaluated on more than 15,000 intraoperative slides across nearly 100 retrospective diagnostic tasks, including benign-malignant discrimination, key intraoperative decision-making, and pan-cancer detection, etc. The model demonstrated robust generalization across 6 institutions, 14 tumor types, and 24 anatomical sites-including previously unseen sites and rare cancers. In a prospective cohort of over 3,000 patients, CRISP sustained high diagnostic accuracy under real-world conditions, directly informing surgical decisions in 92.6% of cases. Human-AI collaboration further reduced diagnostic workload by 35%, avoided 105 ancillary tests and enhanced detection of micrometastases with 87.5% accuracy. Together, these findings suggest that CRISP represents a clinically oriented approach to AI-driven intraoperative pathology, with the potential to support surgical decision-making and facilitate the translation of computational methods into clinical practice. Author information Authors and Affiliations Corresponding authors Supplementary information Supplementary Information (download PDF ) Supplementary Figures 1-7 and Supplementary Tables 1s-6s. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Zhao, Z., Zhou, F., Li, R. et al. A clinically-oriented foundation model for intraoperative pathology. Nat Med (2026). https://doi.org/10.1038/s41591-026-04703-0 Received: Accepted: Published: DOI: https://doi.org/10.1038/s41591-026-04703-0