Introduction: There is an ongoing search for markers of pituitary tumor proliferation and progression that could facilitate further treatment and patient monitoring., Objectives: We studied topoisomerase IIα (topo IIα) expression in different types of pituitary adenomas to evaluate its prognostic value., Patients and Methods: In a retrospective study of 60 patients (mean age, 46.7 ±17.6 y) who underwent pituitary tumor surgery, expression of topo IIα was assessed by immunohistochemistry and compared with histopathological tumor features, clinical symptoms, magnetic resonance imaging, and postoperative tumor recurrence or progression., Results: Expression of topo IIα was observed in 44 of 60 pituitary adenomas (73%). The highest topo IIα index was observed in adrenocorticotropic hormone (ACTH)-secreting tumors (median, 1.13% [0.37-1.21]), followed by silent-ACTH tumors (0.94% [0.89-1.0]), and hormone immunonegative adenomas (0.8% [0.65-1.55]). There were no differences in topo IIα expression with respect to age or sex. Significant correlations were observed between the topo IIα index and tumor size, its invasiveness, abnormal ocular test results, and postoperative tumor recurrence. In patients with a topo IIα index exceeding 1%, we observed a 3.5-fold higher relative risk of tumor recurrence as compared with patients with a topo IIα index lower than 1% (95% confidence interval: 1.8-6.9; P <0.001). Patients with acromegaly who received somatostatin analogues before the surgery had a lower median topo IIα index compared with untreated patients (0%[0-0.22] vs. 0.71% [0.17-1.0]; P <0.05)., Conclusions: In our study group, a topo IIα index exceeding 1% was a prognostic factor for tumor recurrence or progression, especially in patients with hormonally inactive adenomas, which facilitates patient selection for intensive postoperative treatment. Use of somatostatin analogues in acromegaly inhibits topo IIα expression, providing molecular evidence for the effectiveness of these analogues.