Being a relatively common chronic skin condition with understudied pathogenesis, nummular eczema captures attention of medical researchers. The aim of this wok was to describe clinical manifestations of the disease, revise criteria for its accurate diagnosis and understand the role of malfunctioning components of the adaptive and innate immunities in triggering the inflammatory response. Using high-sensitivity ELISA assays, we assessed the cytokine profiles, determined the levels of adhesion molecules and the affinity of serum antibodies in 51 patients with nummular eczema. The immune profiles of the patients were dominated by proinflammatory interleukins, being deficient in regulatory cytokines. The relative abundance of mononuclear CD50+ and CD54+ cells was increased. Natural antibacterial immunity was weakened by the production of lowaffinity serum antibodies. Based on our findings, we have established criteria for the differential diagnosis of nummular eczema and described a contribution of both regulatory and effector immunity components to the abnormal immune homeostasis. We conclude that the discovered defects of the humoral regulation and non-specific resistance in patients with nummular eczema are pathogenic and determine the course of the disease.