Pituitary adenomas are the most common tumors of the sellar region and are, with rare exception, benign neoplasms. The natural history of these lesions is only poorly understood and, although histologic, immunocytologic, and ultrastructural characteristics have been well established, predicting the natural history of individual tumors is, at best, unreliable. In an effort to better characterize pituitary adenomas, we have analyzed the karyotypes of 18 surgical specimens and attempted to correlate with the morphologic appearance and the clinical data, for example, endocrinologic subtypes, histology, and tumor invasiveness. Most hormonal subtypes were studied including seven growth hormone-prolactin (GH-PRL), two Prolactin (PRL), two Adrenocorticotrophin (ACTH), seven nonsecretory (NULL). No correlations with morphology or invasiveness could be made. Of 7 null cell adenomas, five (71%) had normal karyotypes, whereas of 11 hormone-secreting adenomas three (28%) were normal. Of seven tumors with mixed GH-PRL activity, six had abnormal karyotypes. At least three chromosomes harbored abnormalities shared by more than two tumors. The results demonstrate that chromosome abnormalities are also found in benign tumors. These findings, however, suggest that hormone-secreting adenomas may be more likely to be associated with karyotypic abnormalities especially those of the GH-PRL variety. Genetic abnormalities associated with chromosomes 1, 4, 7, and 19 were common and warrant further investigation.