Objective:This study aims to analyze the associations between preoperative serum tumor markers and the micropapillary and solid components in patients with lung adenocarcinoma. Methods:Patients with invasive lung adenocarcinoma who underwent treatment in our department from January 2018 to December 2020 were retrospectively screened. Preoperative serum tumor markers[carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA19-9),carbohydrate antigen 724(CA724),neuron specific enolase(NSE),alpha fetoprotein(AFP)and cytokeratin 21 fragment antigen(CYFRA21-1)],histopathological subtypes and other characteristics were collected. Student’s t-test,χ2 test,logistic regression analyses were used to evaluate the relations between serum tumor markers and the micropapillary and solid components,as well as other clinicopathological characteristics. Results:A total of 2 159 lung adenocarcinoma patients were enrolled in the current study. There were 291 and 248 patients harboring micropapillary and solid components,respectively. Among these six tumor markers,CEA and CYFRA21-1 levels were significantly associated with tumor size and lymph node metastasis(P < 0.001). Patients with solid components had a higher CEA(2.92 ng/mL vs. 1.88 ng/mL,P < 0.001)and CYFRA21-1(2.20 ng/mL vs. 2.02 ng/mL,P < 0.001)level than those absence of solid components. Similarly,the expression levels of CEA(2.59 ng/mL vs. 1.92 ng/mL,P < 0.001)and CYFRA21-1(2.15 ng/mL vs. 2.03 ng/mL,P=0.009)in patients with micropapillary components were significantly higher than that in patients without micropapillary components. The univariate regression analysis indicated that gender,tumor size,CEA and CYFRA21-1 levels were significantly associated with solid and micropapillary components. However,the multivariate analysis showed that associations between CEA and solid(OR = 2.87,95%CI:2.03-4.06,P < 0.001),and micropapillary(OR = 2.36,95%CI:1.68-3.32,P < 0.001) components were still significant,while the associations between CYFRA21-1 and solid or micropapillary components were not significant anymore(P > 0.05). Conclusion:The levels of preoperative serum CEA and CYFRA21-1 were associated with the micropapillary and solid components in lung adenocarcinoma patients,which could serve as predictive factors for the micropapillary and solid components in lung adenocarcinoma.