Artificial intelligence (AI), and more specifically Machine Learning (ML) and Deep learning (DL), has permeated the digital pathology field in recent years, with many algorithms successfully applied as new advanced tools to analyze pathological tissues. The introduction of high-resolution scanners in histopathology services has represented a real revolution for pathologists, allowing the analysis of digital whole-slide images (WSI) on a screen without a microscope at hand. However, it means a transition from microscope to algorithms in the absence of specific training for most pathologists involved in clinical practice. The WSI approach represents a major transformation, even from a computational point of view. The multiple ML and DL tools specifically developed for WSI analysis may enhance the diagnostic process in many fields of human pathology. AI-driven models allow the achievement of more consistent results, providing valid support for detecting, from H&E-stained sections, multiple biomarkers, including microsatellite instability, that are missed by expert pathologists.