Based on favorable outcomes and decreased propensity for lymph node and distant metastasis, multiple ground-glass nodules (GGNs) are now predominantly recognized as early-stage primary independent lung cancer. In this study, we discuss a case involving a patient with reoperative multifocal GGNs who was ultimately diagnosed with early multiple intrapulmonary metastases and multifocal primary lung cancers. This patient exhibited multisite epidermal growth factor receptor (EGFR) mutations, including the classical L858R, exon 19 deletion and the rare V834L variant. Despite a high tumor burden and the presence of various EGFR driver mutations, the patient experienced prolonged dormancy and exceptionally slow lesion growth, even without any systemic treatment. Our research indicates that the patient's immune response against the tumor remained robust throughout the disease course. Furthermore, we found that pathways associated with integrin-mediated cell extracellular matrix adhesion played a role in activating her innate immune responses and regulating tumor dormancy. Our findings suggest that the interplay between cancer cell mutations and the tumor microenvironment (TME) phenotype during tumor evolution contributed to this patient's prolonged survival. Integrating these aspects for lung tumor stratification is expected to improve predictions of growth potential and aid in clinical decision making.