Psoriasis is a chronic complex multisystem, inflammatory, skin disorder that causes vasodilatation and hyperproliferation of keratinocytes, whose clinical expression includes a thickened, erythematous skin, often covered with silver gray scales. Psoriasis is a unique disease where both autoimmune and autoinflammatory responses coexist and the balance between the two components is essential in determining its clinical and histopathological presentation. Adaptive immune responses prevail in chronic plaque psoriasis while innate and autoinflammatory responses predominate in pustular psoriasis. The histopathology of psoriasis is easily recognizable when the disease involves the typical sites such as the extensor surfaces. Although a biopsy is rarely required in case of classic psoriasis, in atypical and controversial conditions, histopathological examination remains the main diagnostic tool that can help in differentiating psoriasis from other dermatoses. In this review, we will discuss the histopathological pictures of the different clinical variants of psoriasis giving some clues to drive the correct diagnosis when the clinical aspects are not enough indicative of the disease.