The Wnt/β-catenin pathway is known to be frequently dysregulated in various human malignancies. Alterations in the genes encoding the components of Wnt/β-catenin pathway have also been described in lung adenocarcinoma. Notably however, the clinical impacts of Wnt/β-catenin pathway alterations in lung adenocarcinoma have not been fully evaluated to date. We here investigated the prognostic implications of single gene variations in 174 cases of surgically resected lung adenocarcinoma tested using targeted next-generation sequencing. Screening of the prognostic impact of single gene alterations identified an association betweenCTNNB1mutation and poor recurrence-free survival inEGFR-mutant LUADs. Based on these results, the entire cohort was stratified into three groups in accordance with the mutational status of Wnt/β-catenin pathway genes (i.e. oncogenicCTNNB1mutation [CTNNB1-ONC], other Wnt/β-catenin pathway gene mutations [Wnt/β-catenin-OTHER], and wild type for Wnt/β-catenin pathway genes [Wnt/β-catenin-WT]). The clinicopathologic characteristics and survival outcomes of these groups were then compared. OncogenicCTNNB1and other Wnt/β-catenin pathway gene mutations were identified in 10 (5.7%) and 14 cases (8.0%), respectively. TheCTNNB1-ONC group cases displayed histopathologic features of conventional non-mucinous adenocarcinoma with no significant differences from those of the other groups. Using β-catenin immunohistochemistry, we found that theCTNNB1-ONC group displayed aberrant nuclear staining more frequently, but only in 60% of the samples. The LUADs harboring aCTNNB1-ONC exhibited significantly poorer RFS outcomes than the other groups, regardless of the β-catenin IHC status. This was a pronounced finding in theEGFR-mutant LUADs only in subgroup analysis, which was then confirmed by multivariate analysis. Nevertheless, no significant OS differences between these Wnt/β-catenin groups were evident. Hence, oncogenicCTNNB1mutations may be found in about 6% of lung adenocarcinomas and may predict post-operative recurrence inEGFR-mutant LUADs. Aberrant nuclear β-catenin staining on IHC appears to be insufficient as a surrogate marker of an oncogenicCTNNB1mutation.