The term "hypereosinophilia of undetermined significance" (HEus) previously known as idiopathic, benign eosinophilia relates to patients who have a long-lasting, unexplained and asymptomatic blood HE. These patients have not been studied so far in terms of demographic characteristics and clinical outcome. The aim of this study was to present the clinical characteristics and outcome of HEus patients. This is a retrospective, single-center study of 40 patients with HEus. All patients underwent the basic and specialized evaluations in order to rule out the most common causes of blood HE, but no abnormalities were detected. Twelve patients with at least moderate blood hypereosinophilia (defined as greater than 3.0 × 10(9)/L) for more than 1-year duration were treated with corticosteroids (CS) to avoid end-organ damage. Twenty-one patients (52 %) had an increased leukocyte count at diagnosis. Median blood eosinophilia was 4.2 × 10(9)/L (range 1.5-55.4). HE > 3.0 × 10(9)/L was demonstrated in 17 patients. 65 % of studied population had an increased serum IgE levels, whereas only 2 % demonstrated an increased serum vitamin B12 levels. A median bone marrow infiltration by eosinophils was 30.5 % (range 11-78.2). All treated patients responded promptly to CS and remained in complete remission while receiving low doses of CS (20 mg/day to 5 mg every 2-day). One patient developed hypereosinophilic syndrome (HES) after 11 years of follow-up. Further studies are needed to define risk factors of HES development. The use of CS for HEus patients is controversial and should be individualized.