Objective: To review the clinical utility of measuring serum α-subunit as a marker for residual tumor in a group of patients with surgically resected nonfunctional pituitary adenomas. Methods: In this retrospective cross-sectional chart review using the pituitary database at the Cleveland Clinic, we identified patients with nonfunctional pituitary macroadenomas over a 4-year period (2000-2004) and selected those patients who had an elevated α-subunit concentration measured before pituitary surgery. Presurgery and postsurgery measurements of α-subunit, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone were documented. Findings from preoperative and postoperative pituitary magnetic resonance imaging (MRI) were reviewed. Results: We identified 54 patients who were evaluated for nonfunctional pituitary macroadenomas during the study period. Of the 39 who underwent pituitary surgery, 34 had a serum α-subunit concentration measured before surgery. Eight of 34 patients had elevated preoperative α-subunit levels with a median value of 1.8 ng/mL (range, 1.0-3.4 ng/mL). Of the 8 patients, 7 had follow-up MRI a median of 12 months (range, 6-52 months) after surgery. One patient was lost to follow-up. Three of 7 patients had persistently elevated α-subunit levels postoperatively; in 2 of these 3, MRI did not identify residual tumor. Among the 4 patients with postoperative normalization of α-subunit, 2 patients had residual tumor on MRI. Conclusion: The discrepancy between α-subunit levels and postoperative MRI calls into question the value of routine α-subunit measurement as a tumor marker in patients with nonfunctional pituitary macroadenomas.