https://github.com/dazhangyu123/ACMIL}.
Overfitting remains a significant challenge in the application of Multiple Instance Learning (MIL) methods for Whole Slide Image (WSI) analysis. Visualizing heatmaps reveals that current MIL methods focus on a subset of predictive instances, hindering effective model generalization. To tackle this, we propose Attention-Challenging MIL (ACMIL), aimed at forcing the attention mechanism to capture more challenging predictive instances. ACMIL incorporates two techniques, Multiple Branch Attention (MBA) to capture richer predictive instances and Stochastic Top-K Instance Masking (STKIM) to suppress simple predictive instances. Evaluation on three WSI datasets outperforms state-of-the-art methods. Additionally, through heatmap visualization, UMAP visualization, and attention value statistics, this paper comprehensively illustrates ACMIL's effectiveness in overcoming the overfitting challenge. The source code is available at \url{