The distinction between pleuritis and sarcomatoid mesothelioma represents an extremely complex challenge in pathological anatomy due to the morphological similarity between the two conditions. Pleuritis is an inflammation of the pleura, often caused by infections, trauma, or other medical conditions, whereas sarcomatoid mesothelioma is a rare and aggressive form of cancer affecting the pleura, often associated with asbestos exposure. Correct diagnosis is crucial to ensure adequate treatment, as the two conditions have very different prognoses and therapeutic approaches. Histopathological analysis is currently based on Whole Slide Images (WSI) and requires careful evaluation by expert pathologists, who must thoroughly examine cellular and tissue characteristics to distinguish between these two entities.