〔Abstract〕 Objective To explore the spatial and temporal heterogeneity of pathological phenotype of epidermal growth factor receptor(EGFR)-mutant transformed locally advanced or metastatic small-cell lung cancer(SCLC) or neuroendocrine carcinoma(NEC). Methods This study retrospectively analyzed EGFR-mutant LUAD patients who were treated with EGFR-TKIs and underwent a transformation into SCLC/NEC. Baseline clinicopathological characteristics after initial transformation were summarized. According to the different pathological components of initial SCLC/NEC transformation, it was defined as incomplete transformation and complete transformation. Incomplete transformation was defined as three categories: intratumoral transformation, intertumoral transformation and effusional transformation. Results This study collected 49 patients who met the criteria. Among forty-nine patients, incomplete transformation was 34.7%(17/49) and complete transformation was 65.3%(32/49). In addition, intratumoral transformation, intertumoral transformation and effusional transformation were respectively 82.3%(14/17), 5.9%(1/17) and 11.8%(2/17).It was mean that the spatial heterogeneity of pathological phenotype of initially transformed SCLC/NEC was 34.7%. After initial transformation, among the fifteen patients in dynamic histological and/or cytological biopsies, the temporal heterogeneity of pathological phenotype of initially transformed SCLC/NEC was 46.7%(7/15). In addition, there was no significant difference in first-line treatment post-transformation progression-free survival and post-transformation overall survival between incomplete transformation group and complete transformation group. Conclusion EGFR-mutant transformed locally advanced or metaststic SCLC/NEC has spatial and temporal heterogeneity in pathological phenotype.