Noninfectious cutaneous granulomas, particularly in an acral distribution, may be an early sign of mixed cellular and humoral immunodeficiency. Special stains of skin biopsy sections and cultures for bacteria, acid-fast bacilli, and fungi are important in eliminating the possibility of underlying pathogens. In three children with combined immunodeficiency and cutaneous granulomas, the administration of moderate- to high-dose systemic corticosteroids was the most effective therapy. However, careful consideration should be given before administering systemic corticosteroids to an immunocompromised patient.