〔Abstract〕 To investigate the correlations among clinicopathological features , histopathological growth patterns and prognosis of extrapulmonary multiple metastatic (stage ⅣB) pulmonary adenocarcinoma with epider- mal growth factor receptor (EGFR) mutations . Methods A total of 488 eligible patients with adenocarcinoma of stage ⅣB from the First Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of Universi- ty of Science and Technology of China were collected . Clinicopathological data , EGFR gene mutation subtypes , metastatic sites , histopathological growth patterns and survival information were collected . The chi-square test ( χ2 test ) and Fisher exact probability method were used to detect the correlation between the metastasis status and va- rious clinical characteristics; the Kaplan-Meier method was used to conduct survival analysis on the median Pro- gression-Free Survival (PFS) under different clinical characteristics . Cox univariate and multivariate regression an- alyses were conducted to evaluate the impact of various clinical characteristics on prognosis . Results The metastat- ic patterns of stage Ⅳ B pulmonary adenocarcinoma with EGFR mutations was correlated with histopathological growth patterns (P < 0. 05) . In the group with multiple metastases in a single organ , the proportion of micropapil- lary type in the group with multiple metastases in a single organ was higher than that in the group with multiple-or- gan metastases (51 . 1% vs 41 . 1% ) , while the proportion of solid type in the group with multiple-organ metastases was higher than that in the group with multiple metastases in a single organ (23 . 8% vs 14. 2% ) . Multiple brain or multiple bone metastases were correlated with histopathological growth patterns and tumor differentiation degree . Compared with the multiple bone metastases group , the proportion of acinar type decreases in the multiple brain metastasis group , while the proportion of micropapillary type increased . Moreover , the proportion of poorly differen- tiated tumors increased significantly (P < 0. 05) . Compared with multiple bone metastases , the proportion of poorly differentiated tumors significantly increases in the group with multiple brain metastases . The median progression- free survival (PFS) of patients with a predominant solid growth pattern was shorter than that of patients with other growth patterns ( 12. 7 months vs 17. 8 months , P < 0. 05) . The PFS of patients in the poorly differentiated group was worse than that in the moderately differentiated group (15 . 6 months vs 17. 8 months , P < 0. 05) . There were significant differences in PFS among patients with common sensitive mutations and rare mutations EGFR ( 17. 3 months vs 10. 2 months , P < 0. 005) . Cox proportional hazards regression model suggested that solid growth pat- tern , poor differentiation and rare single gene mutation were adverse prognostic factors . Conclusion In stage ⅣB pulmonary adenocarcinoma patients with EGFR mutations , both the metastatic patterns and metastatic sites are sig- nificantly correlated with the histopathological growth patterns of tumors . Moreover , the EGFR mutation subtypes as well as the histopathological growth patterns and differentiation degree of tumors significantly affect the prognosis of patients .