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．Incom- plete transformation was defined as three categories : intratumoral transformation，intertumoral transformation and ef- fusional 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-trans- formation 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.