Immunofluorescence (IF) microscopy has been used for decades as a diagnostic tool in autoimmune skin diseases and hereditary bullous dermatoses. In 1942, Coons et al. described the first use of IF staining, by using fluorescent dye-labeled antibodies to detect pneumococcal antigens in tissues from infected mice [1,2]. Using indirect IF, Beutner and Jordon were the first to demonstrate autoantibodies in the sera of patients with pemphigus vulgaris (PV) . In addition, during the early 1960s, IF techniques were applied to the study of collagenoses. Using direct IF analysis of biopsies from patients with lupus erythematosus (LE), Burnham et al. and Cormane described a band of immunoglobulin (Ig) deposits at the dermal–epidermal junction (DEJ) in lesions and normal-appearing skin, respectively [4,5]. At around the same time, the binding patterns of the antinuclear antibodies (ANAs) in LE were characterized [6,7]. Based on these initial studies, complement staining methods were established to demonstrate the complement-fixing activity of autoantibodies [8–11]. Historically, the IF method has played an important role not only in understanding the immunological basis of diseases, but also in the identification of new disorders. Thus, the IgA staining pattern using direct IF served as the major feature for differentiating between linear IgA disease and dermatitis herpetiformis (DH; or Duhring’s disease), two clinically overlapping bullous diseases [12–14].