GNAS1 mutations were absent in all the studied AIPmut-positive somatotropinomas (n = 23) but were detected in 50% of the AIPmut-negative familial somatotropinomas (5 of 10), 16.7% of the AIPmut-negative, young-onset cases (1 of 6), and 26.3% of the unselected acromegaly cases studied (5 of 19). Here, GNAS is linked to growth hormone-producing pituitary gland neoplasm.