Hyperimmunoglobulin E syndrome (HIES) is an immunodeficiency associated with chronic dermatitis, recurrent dermal and pulmonary infections, skeletal abnormalities and increased immunoglobulin E (IgE). It is diagnosed through a score that has to accumulate over time as they appear. This paper reports three clinical cases as a sample of the high clinical suspicion necessary for the search of the diagnostic criteria, and the accumulation of progressive evidence over time. The treatment is only symptomatic and the prognosis is still unclear.