# Uncertainty Estimation in Pathology Foundation Models via Deep Mutual Learning

arXiv: https://arxiv.org/abs/2606.30020 · HTML: https://mlsanity.com/paper/2606.30020/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 23 of its 46 references that are in the map.
- First posted on arXiv 29 Jun 2026.

## Builds on (most cited first, 23 of 23)

- [Dropout as a Bayesian Approximation: Representing Model Uncertainty in Deep Learning](https://mlsanity.com/paper/1506.02142/) (2015)
- [Simple and Scalable Predictive Uncertainty Estimation using Deep Ensembles](https://mlsanity.com/paper/1612.01474/) (2016)
- [Optuna: A Next-generation Hyperparameter Optimization Framework](https://mlsanity.com/paper/1907.10902/) (2019)
- [CoCa: Contrastive Captioners are Image-Text Foundation Models](https://mlsanity.com/paper/2205.01917/) (2022)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Evidential Deep Learning to Quantify Classification Uncertainty](https://mlsanity.com/paper/1806.01768/) (2018)
- [Deep Mutual Learning](https://mlsanity.com/paper/1706.00384/) (2017)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [Simple and Principled Uncertainty Estimation with Deterministic Deep Learning via Distance Awareness](https://mlsanity.com/paper/2006.10108/) (2020)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [HEST-1k: A Dataset for Spatial Transcriptomics and Histology Image Analysis](https://mlsanity.com/paper/2406.16192/) (2024)
- [PRISM: A Multi-Modal Generative Foundation Model for Slide-Level Histopathology](https://mlsanity.com/paper/2405.10254/) (2024)
- [Accelerating Data Processing and Benchmarking of AI Models for Pathology](https://mlsanity.com/paper/2502.06750/) (2025)
- [A Clinical Benchmark of Public Self-Supervised Pathology Foundation Models](https://mlsanity.com/paper/2407.06508/) (2024)
- [Hibou: A Family of Foundational Vision Transformers for Pathology](https://mlsanity.com/paper/2406.05074/) (2024)
- [Gramian Multimodal Representation Learning and Alignment](https://mlsanity.com/paper/2412.11959/) (2024)
- [Benchmarking foundation models as feature extractors for weakly-supervised computational pathology](https://mlsanity.com/paper/2408.15823/) (2024)
- [Fusion of Multi-scale Heterogeneous Pathology Foundation Models for Whole Slide Image Analysis](https://mlsanity.com/paper/2510.27237/) (2025)
- [Ensemble learning of pathology foundation models for precision oncology](https://mlsanity.com/paper/2508.16085/) (2025)
- [SGPMIL: Sparse Gaussian Process Multiple Instance Learning](https://mlsanity.com/paper/2507.08711/) (2025)
- [GrapHist: Graph Self-Supervised Learning for Histopathology](https://mlsanity.com/paper/2603.00143/) (2026)

## Abstract (arXiv)

Pathology foundation models (PFMs) offer generalizable representations for whole-slide image (WSI) analysis, yet their clinical adoption remains limited. Specifically, their predictions lack reliable confidence estimates, and no single PFM is universally best across tasks, which severely undermines trust in medical settings. To overcome this, we propose DICE, a plug-and-play framework that ensembles K frozen PFMs and estimates uncertainty based on their consensus. We align the ensemble members via deep mutual learning and theoretically show that this objective controls an upper bound on epistemic uncertainty. Additionally, we demonstrate that the ensemble localizes abnormalities at the patch level without any explicit supervision. We evaluate DICE on three challenging WSI benchmarks. Notably, our framework provides reliable uncertainty estimates that accurately flag failure-prone cases under in- and out-of-distribution settings, while matching or outperforming SOTA baselines in classification, calibration, and localization. Overall, DICE takes a crucial step toward translating PFMs into uncertainty-aware decision-support systems.