Notably, when the SHOX2 and RASSF1A methylation panel was combined with cytology, the AUC improved to 0.809 (95% CI: 0.7656–0.8527), and the sensitivity and specificity were 74.7% and 87.1%, respectively, suggesting that SHOX2 and RASSF1A methylation detection of BFF/BALF could be an effective complementary tool of cytology in lung cancer diagnosis. Here, SHOX2 is linked to lung carcinoma.