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Mucocutaneous diseases may frequently present diagnostic dilemma as their diagnosis depends on their oral and cutaneous manifestations, histopathology, IHC, etc. Mucocutaneous diseases cannot be differentiated clinically and histopathologically from other disorders. Therefore the need of immuno-fluorescent studies have occurred as it is a reliable biochemical staining technique for the detection of antibodies, which are bound to antigen in the tissue or in circulating body fluids. The relative simplicity and accuracy of the technique has made immune-fluorescence a powerful technique in the diagnosis of mucocutaneous diseases. Thus, immuno-fluorescence has become an essential component of today’s diagnostic laboratory. The two main methods of immuno-fluorescent labelling are direct and indirect.