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 (CEA、CA19-9、CA724、NSE、AFP and 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 2159 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). LUAD 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 LUAD 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 LUAD patients, which could serve as predictive factors for the micropapillary and solid components in LUAD.