Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinemia, poor antibody responses, and recurrent bacterial infections, usually of the sinorespiratory tract. A not uncommon complication is granuloma of the lungs, spleen, liver, and/or skin. We report the case of an 18-year-old boy with CVID and chronic granulomas of the left arm (since 13 years of age) refractory to treatment with antibiotics, intravenous immunoglobulin, antifungal agents, systemic and intralesional steroids, IFN-gamma, cyclosporine, methotrexate, hydroxychloroquine, localized radiation therapy, and surgical excision. The lesions improved after treatment with the systemic administration of the TNF-alpha inhibitor etanercept for 1 year. Etanercept prevents soluble TNF from binding to its cell membrane receptor, leading to inhibition of its inflammatory cascade. We recommend further trials of etanercept in patients with CVID with noninfectious recalcitrant granulomas.