Inflammatory radicular cysts (IRCs) are chronic lesions that follow the development of periapical granulomas (PGs). IRCs result from multiple inflammatory reactions led initially by several pro-inflammatory interleukins and growth factors that provoke the proliferation of epithelial cells derived from epithelial cell rests of Malassez present in the granulomatous tissue, followed by cyst formation and growth processes. Multiple theories have been proposed to help explain the molecular process involved in the development of the IRC from a PG. However, although multiple studies have demonstrated the presence of epithelial cells in most PGs, it is still not fully understood why not all PGs turn into IRCs, even though both are stages of the same inflammatory phenomenon and receive the same antigenic stimulus. Histopathological examination is currently the diagnostic gold standard for differentiating IRCs from PGs. Although multiple studies have evaluated the accuracy of non-invasive or minimally invasive methods in assessing the histopathological nature of the AP before the intervention, these studies' results are still controversial. This narrative review addresses the biological insights into the complex molecular mechanisms of IRC formation and its histopathological features. In addition, the relevant inflammatory molecular mediators for IRC development and the accuracy of non-invasive or minimally invasive diagnostic approaches are summarised. (EEJ-2022-03-041).