Non-functional pituitary adenomas (NFPAs) account for 80% of pituitary adenomas with the majority of these exhibiting recurrences post-surgery. Overexpression of beta-catenin and c-myc is common in numerous invasive tumors. The present study sought to investigate the correlation of beta-catenin and c-myc expression levels with aggressive growth and recurrence of NFPAs, using immunohistochemical examination of tissue microarrays. Tissue microarrays comprised 212 NFPAs specimens and 10 healthy specimens as controls. NFPAs were categorized as non-aggressive or aggressive. Immunohistochemical examination was performed to determine the expression of beta-catenin and c-myc. Correlation of the expression levels of beta-catenin and c-myc with clinicopathological parameters, including aggressiveness and recurrence, were assessed by univariate, multivariate and logistic regression analysis. Increased expression of beta-catenin and c-myc was detected in the majority of aggressive NFPAs specimens (71.1 and 88.7%, respectively). There was a significant positive correlation between beta-catenin and c-myc expression and aggressiveness [P=0.001, Odds Ratio (OR)=4.011; P<0.001, OR=30.833]. Only beta-catenin expression demonstrated a significant correlation with recurrence in NFPAs (P=0.021, OR=2.571). beta-catenin and c-myc were demonstrated to be potential biomarkers for aggressive NFPAs and in the future, beta-catenin may serve as a marker for aggressive behavior and recurrence in NFPAs.