Until now, no method has been available to discriminate mature plasmacytoid DC (pDC) from myeloid DC (mDC) immunohistochemically. In this study, we report that these DC-subsets can be distinguished in routine pathological sections. Immature and mature monocyte-derived DCs (MoDCs) were S100 calcium binding protein B (S100B)⁺, while pDCs generated from pDC-precursors were S100B^-. In contrast, both mature MoDC and pDC were fascin⁺. Epidermal Langerhans cells (LCs) were S100B⁺/fascin^-. Although the majority of DCs were S100B⁺/fascin⁺ in the dermis with nonspecific inflammation, dermal DCs were mostly S100B^-/fascin⁺ in psoriasis vulgaris, in which type I interferon secreted by pDC-precursors is thought to play a major role. S100B⁺/fascin⁺ DCs were accumulated in the superficial lymph node (LN), while they were scarce in the deep LN. In the superficial LN with dermatopathic lymphadenitis, a large number of S100B⁺/fascin⁺ DCs were accumulated in the T-zones, where numerous LC-derived DCs are accumulated. In contrast, almost all DCs were S100B^-/fascin⁺ in the superficial LN with Kikuchi's lymphadenitis, in which numerous pDC-precursors are known to be present. In contrast to the superficial LN, the deep LN contained numerous S100B^-/fascin⁺ DCs and a few S100B⁺ DCs. Thus, the distributions of S100B⁺ DC or S100B^-/fascin⁺ DC correspond to the putative distribution of mDC or mature pDC, respectively. [J Clin Exp Hematopathol 49(1) : 23-31, 2009]