Inflammatory disorders of the skin, including eczematous, psoriasiform, lichenoid-interface, autoimmune, and neutrophilic dermatoses, probably represent the group of cutaneous diseases in which molecular pathology currently has the least impact in daily clinical practice. Many of these diseases are readily diagnosed through the correlation of clinical features with histopathological findings on hematoxylin and eosin (H + E)-stained tissue sections. In general, microscopic pattern analysis offers a very useful and reliable method to diagnose inflammatory skin diseases. The application of additional histochemical stains, immunohistochemistry, and/or immunofluorescence analysis is occasionally required. However, in some instances, diagnostic difficulties do arise. For example, the clinical and/or microscopic distinction of allergic contact dermatitis (ACD) from irritant contact dermatitis (ICD), pompholyx (dyshidrotic eczema) from pustular psoriasis, and even classic chronic psoriasis from chronic atopic dermatitis (AD) may be challenging. Although chronic psoriasis and AD show distinct differences with respect to cytokine milieu (i.e., Th1 in AD vs. Th2 in psoriasis), bacterial superinfection, surface pH, transepidermal water loss and itch, it is well known that these disorders share many morphological and molecular features [1, 2]. For example, from a dermatopathologist’s perspective, the lesional skin of both conditions can demonstrate the presence of T-cell and CD1a+/CD11c+ dendritic cell infiltrates associated with hyperplasia/altered differentiation of keratinocytes [1, 2]. In addition, cutaneous T-cell dyscrasias (i.e., lymphomas) can occasionally masquerade, both clinically and histopathologically, as inflammatory dermatoses (i.e., cutaneous lupus erythematosus) [3–5].