Background: Pityriasis rosea (PR) is well established as a distinctive inflammatory disease of the skin. Detailed studies of histopathologic characteristics and immunophenotype of the infiltrates, however, are sparse. Objectives: To reassess histological criteria of PR and to characterize the infiltrate immunohistochemically. Methods: Thirty-four patients were included in the study. Clinical features and histopathology were reassessed and compared with those of allergic contact dermatitis and seborrheic dermatitis. Immunohistochemical stainings with CD3, CD20, CD4, CD8, CD1a, CD68, CK 16, Bcl 2, and Ki67 were performed. Results: Multifocal spongiosis, mounds of parakeratosis, simulators of Pautrier's microabscesses, and a superficial perivascular infiltrate with sparse spillage into the interstitium are typical of PR. Necrotic keratinocytes are an inconsistent finding, vacuolar alteration is absent. Immunhistochemical results indicate that the epidermal spongiosis is mediated by CD8 positive lymphocytes and CD1a positive Langerhans cells together with CD68 positive histiocytes, while B lymphocytes and plasma cells are absent from the infiltrate and CD4 positive lymphocytes remain largely in the dermal infiltrate. Conclusions: PR has distinct histological features enabling distinction from other forms of spongiotic dermatitides. Pathogenetically, CD8 positive lymphocytes and CD1a positive Langerhans cells seem to be chiefly involved in the specific spongiotic process of PR.