“…SCCis shows the following RCM features ( 14 ) ( Figures 1A, C ): i) at the level of stratum corneum, highly refractive amorphous structures and sporadically polygonal, nucleated cells; ii) at the level of the stratum granulosum/spinosum, marked architectural disarray, consisting of keratinocytes highly variable in size, shape, and nuclear morphology; scattered bright dendritic cells may also be found; iii) at the level of the dermoepidermal junction, large rounded dark areas, corresponding to enlarged dermal papillae. Horizontal histopathology perfectly matches with the previous reported RCM findings ( 14 ) ( Figures 1B, D ): hyperkeratosis and parakeratosis are the histopathological causes of the refractive amorphous structures and the nucleated cells observed in the stratum corneum at RCM; the loss of architectural array visible in the stratum granulosum/spinosum at RCM reflects the presence of atypical keratinocytes with nuclei of variable size and shape along the entire thickness of epidermis; some S-100 positive, CD1a negative and Melan-A negative dendritic cells may be occasionally found scattered among the neoplastic cells; lastly, at the dermoepidermal junction, HHSs show enlarged dermal papillae containing glomeruloid capillary vessels, corresponding both to the rounded dark areas and to the “red dots” observed at RCM and dermoscopy, respectively. Since the horizontal histopathology does not allow to evaluate the possible presence of dermal invasion, the concept that its use is only for the purpose of comparing it with the RCM findings, in order to further validate the diagnostic use of RCM, must be emphasized.…”