Severe asthma is a challenging disease, and omalizumab has been an important tool to help clinicians address more efficiently this problem. Besides reduction of free and total serum IgE levels, there are a number of other immunologic effects of omalizumab that may be of relevance in its therapeutic action. We report two mite-allergic severe asthmatic patients successfully treated with omalizumab for one year. Clinically, patients improved gradually, with no further need for systemic steroids or emergency department visits during that treatment period, and with Asthma Control Test (ACT) scores showing controlled disease, although pulmonary function didn't show any significant improvement. Immunologically, we observed marked down-regulation of surface IgE and FcεRI on basophils, plasmacytoid and myeloid dendritic cells, as well as a reduction of basophil activation after specific allergen stimulation. These effects were clearly evident immediately after one month but were enhanced at 3, 6 and 12 months of omalizumab treatment, suggesting an advantage to continuing this therapy, and raising the hypothesis of some markers being useful to assess immunological responses to omalizumab, which could assist in the clinician's decision to stop or to restart this treatment.