A new lung adenocarcinoma classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) has recently been published. However, the relationship between EGFR mutations and subtype of adenocarcinoma remains unclear. A total of 161 surgically resected lung adenocarcinomas in Zhejiang Cancer Hospital were reviewed using the new classification system. Epidermal growth factor receptor (EGFR) mutations were observed in 67 cases (41.6 %). EGFR mutations were found to be closely associated with the micropapillary predominant subtype (P = 0.0068) and lepidic component (P = 0.005). The frequency of EGFR mutation was found to be lower in the solid predominant subtype than other subtype (P = 0.04). In conclusion, histologic subtyping was found to be associated with EGFR mutations. The EGFR mutation frequency of micropapillary and lepidic predominant subtypes was found to be more pronounced than that of other subtypes.