<p>Lung adenocarcinoma currently represents the most prevalent subtype of lung cancer and a leading cause of cancer-related mortality worldwide. Accurate and early diagnosis is critical for improving patient outcomes, yet traditional histopathological assessment is time-consuming and dependent on pathologist expertise. We present a deep learning approach based on convolutional neural networks that achieves a 0.974 accuracy in the automatic classification of lung adenocarcinoma, squamous cell carcinoma, and normal tissue from histological images, which serves as the baseline for a novel quantitative framework evaluating model-attention heatmaps. To address the explainability challenges of deep learning in real-world clinical settings, we consider the adoption of several Class Activation Mapping techniques i.e., Gradient-weighted Class Activation Mapping, Gradient-weighted Class Activation Mapping++, Score-Weighted Class Activation Mapping, and Fast Score-Weighted Class Activation Mapping, to generate visual explanations behind the model’s predictions. To achieve this, we introduce a quantitative evaluation framework using Mean Squared Error, Root Mean Squared Error, Peak Signal-to-Noise Ratio, and Structural Similarity Index Measure. This framework confirms that the combination of Gradient-weighted Class Activation Mapping++ and Score-Weighted Class Activation Mapping produces the most consistent and structurally faithful heatmaps, with Structural Similarity Index Measure values of 0.94 for lung adenocarcinoma. By combining high diagnostic accuracy with qualitative visual insights, the proposed quantitative XAI validation framework aims to provide an explainable and consistent decision-support tool for pathologists, facilitating visual indication of model-attended regions contributing to the prediction within histological images.</p>