Pathology is the science of how a tissue changes during the process of the disease. The pathology is of important knowledge for understanding subsequent treatment concepts of a disease. In the cariology field, pathological features of caries are often presented using tooth sections, whereby the sequence and spread can be monitored. It is optimal to describe such changes using thin undecalcified tooth sections as an overview can be given of both enamel demineralization and pulp-dentine reactions. Also, an optimal understanding is achieved if the clinical status of carious lesion activity is known. Different studies using human teeth have shown the principle changes in progressive stages of carious lesions; the growth of the enamel lesion reflects the growth condition of the cariogenic biofilm. Surprisingly, the pulp (the odontoblast) is aware of the cariogenic stimuli even before mineral alteration has taken place within the dentine. The microorganisms mainly invade the dentine during enamel cavitation. In this chapter, the current improvement of knowledge on advanced carious lesions has been assessed in detail both histologically and radiographically. From a radiographic point of view, well-defined deep and extremely deep carious lesions and their difference are presented. Recent advances in artificial intelligence (AI) in medicine have raised the possibility of increasing the accuracy and speed of histopathological examination techniques. However, the literature involving AI-based histopathological features of hard and soft dentinal tissue pathologic changes is still scarce.