The identification of a specific molecular marker for aggressiveness of nonfunctioning pituitary adenomas (NFPAs) is urgently required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, low expression of secreted frizzled-related protein 2 (sFRP2) in NFPAs was demonstrated by reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemical analyses. The results confirmed an abnormal accumulation of free beta-catenin in the nuclei of NI Pas, which is the core step for the activation of the Wnt canonical signaling pathway. Furthermore, cyclin D1 and c-Myc, the downstream proteins of the Wnt canonical signaling pathway, were overexpressed in aggressive NEPAs. These findings demonstrated the activation of the Wnt canonical signaling pathway- in aggressive NEPAs. In addition, sFRP2 expression was observed to be inversely correlated to the aggressiveness of NFPAs. Therelime, sFRP2 may act as a tumor suppressor through modulation of the cellular cytosolic pool of P-catenin in NEPAs. Furthermore, the expression of sFRP2 may serve as a biomarker for NFPAs aggressiveness and prognosis.