Psoriasis is an immune-mediated disease which affects a large world population. It has long been considered a dermatological disorder in which keratinocytes and lymphocytes play a relevant pathogenic role. The aim of our study is to more closely observe and better define the role of dendritic cells (DCs) in psoriasis. We made a comparative analysis of the antigenic profile and the number, by immunohistochemical and electron microscopical study, of skin biopsy samples from psoriatic patients before and 4 months after biological treatments. Our results demonstrate an abundant distribution of activated DCs in lesional skin of psoriatic plaques and a marked decrease after biological therapies, a decrease of 70 percent for Langerhans cells (LCs) and mature myeloid dendritic cells (mDCs) and of 50 percent for plasmocytoid dendritic cells (pDCs). Both previous reports and the results of the present study support an underlying persistent immune response involving DCs in the onset and persistence of psoriasis. As DCs play a pivotal role in pathogenesis of psoriasis by presenting antigens via major histocompatibility complex class (MHC) II molecules, the present study supports the view that biological therapies are also effective in clearing psoriatic lesions as well as in reducing the number of DCs.