In this study, measurement of tumor markers was included in the clinical evaluation for patients, which mainly included CEA, NSE, CYFRA21-1, SCC-Ag, and CA125 that were highly related to benign or malignant SPNs, of which CEA, CYFRA21-1, and CA125 presented significant differences in the univariate analysis, and the results of multivariate logistic regression analysis concluded that CYFRA21-1 could be the independent risk factor for developing lung adenocarcinoma lesion from SPN, and that the elevated CYFRA21-1 level might reflect SPN progression. The gene discussed is ENO2; the disease is lung adenocarcinoma.