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There is considerable clinical and histological overlap among the subepidermal autoimmune bullous diseases. The knowledge at the molecular level of the dermo-epidermal junction is essential to understand this group of diseases. The immune-based techniques have contributed to increase the knowledge of these entities and have been progressively incorporated into clinical practice. In this review of the diagnostic methods of subepidermal autoimmune bullous diseases we summarize the most recent advances on the molecular biology of the dermo-epidermal junction, focusing on the immune-based diagnostic techniques. We distinguish two main groups of diagnostic methods: those that detect autoimmune deposits in the skin (direct immunofluorescence and its variants including confocal microscopy) and those that detect antibodies in serum or in other fluids (indirect immunofluorescence and its variants, ELISA, immunoblot and immunoprecipitation). We explain the methodology and diagnostic keys of the techniques most widely applied in our milieu.