Although dermatopathology and molecular biology are often considered to be separate laboratory disciplines, the respective approaches are far from mutually exclusive. This is certainly the case for understanding the pathology of blistering skin diseases, both acquired and inherited. For example, in toxic epidermal necrolysis, dermatopathology in isolation may provide few clues to disease pathogenesis. There is widespread keratinocyte apoptosis and a variable infiltrate of cytotoxic T cells, but morphology alone offers little insight into what causes the epidermal destruction. In contrast, molecular biology studies have revealed several key processes that help explain the keratinocyte death, including increased expression of death receptors and their ligands on keratinocyte cell membranes as well as the presence of local or systemic immunocyte-derived cytolytic granules. For some inherited blistering diseases, however, such as epidermolysis bullosa, the molecular pathology is complex and difficult to unravel in isolation, yet the addition of dermatopathology is helpful in focusing molecular investigations. Notably, immunolabelling of cell adhesion proteins using specific antibody probes can identify reduced or absent immunoreactivity for candidate genes/proteins. Bridging dermatopathology and molecular biology investigations facilitates a greater understanding of disease processes, improves diagnostic accuracy, and provides a basis for the development and appraisal of new treatments.