Primary immunodeficiency diseases (PIDs) are rare but important conditions found predominantly in children. We studied PIDs in a large pediatric hospital, their association with cutaneous alterations, and the importance of cutaneous alterations as diagnostic markers. Among 382,383 pediatric patients, 130 (0.0003%) had a PID: humoral in 27, cellular and combined in 18, phagocytic in 37, and associated with major defects in 45. An average of two cutaneous alterations were present in 90 (69%) patients: infections in 80, eczema-dermatitis in 38, and miscellaneous in 57. In 71 (79%) patients the cutaneous alterations preceded and were the basis for the clinical immunologic diagnosis. Only two PIDs were not associated with cutaneous lesions.