Because most boys with Klinefelter syndrome appear similar to boys with normal karyotypes, the disorder typically is identified in adulthood, when infertility or gynecomastia are common presentations. However, by this time, a therapeutic window during adolescence for treatment of hypogonadism, cognitive impairments, and psychosocial factors has been missed. Late or incomplete puberty should prompt further examination. Testicular size can be measured with a Prader orchidometer or ultrasonography. Middle school–age boys with Klinefelter syndrome often will have elevated follicle-stimulating and luteinizing hormone levels and low plasma testosterone levels. Subclinical values on laboratory indices may be found in these patients; therefore, a karyotype with instructions to count sex chromosomes in 50 cells is useful for diagnosis, especially in patients with mosaicism.