Objective: The aim of this study was to investigate the clinical significance of Ki-67 proliferation index and p53 gene expression in the pre-operative and post-operative evaluation of pituitary macroadenomas. Material and Methods: We retrospectively evaluated 81 pituitary macroadenoma patients, where pre-operative, six-month and one-year follow-up post-operative dynamic contrastenhanced magnetic resonance imaging examinations were present in our picture archiving and data system. All patients underwent surgical tumor removal and were pathologically diagnosed as having macroadenomas. Results: In Ki-67 positive macroadenoma cases, maximal tumor diameter was found significantly higher than in Ki-67 negative adenoma cases. When tumor invasiveness was compared based on Hardy's classification with the Ki-67 proliferation index values of macroadenomas, no statistically significant correlation was found between tumor invasiveness and Ki-67 values. We can state that there is a strong correlation between Ki-67 positiveness and increase in residual tumor dimensions. In p53 negative and positive macroadenoma cases, there was no significant correlation between p53 gene expression and maximal tumor diameter. When we compared the tumor invasiveness was compared based on Hardy's classification with the p53 gene expression of macroadenomas, no statistically significant correlation was found between tumor invasiveness and p53 values. We can say that there is a strong correlation between p53 gene expression positiveness and increase in residual tumor dimensions. Conclusion: Ki-67 proliferation index and p53 gene expression level determination of macroadenomas and their association with the hormone profiles, invasiveness, preoperative primary tumor and post-operative residual tumor dimension parameters can be combined in order to predict early tumor progression and patient prognosis.