Background: Recently, an increasing number of cases with transformation from lung adenocarcinoma to small cell lung cancer (SCLC) have been identified, but few studies have investigated the clinical, pathological as well as molecular characteristics of these cases. This study aimed to summarize and analyze these features. Methods: We retrospectively collected data including clinical information, laboratory examination results, radiological and pathological findings of ten patients, who were confirmed to undergo SCLC transformation following treatment from January 2014 to January 2020. Results: The median time of treatment (targeted agents) was 14 months, and the median time interval of SCLC transformation following treatment was 24 months. Immunohistochemical indicators after transformation showed positive thyroid transcription factor 1 (TTF1), synaptophysin (Syn), CD56, and AE1/AE3, highly expressed Ki67, as well as negative programmed cell death-ligand 1 (PD-L1). Compared with the patients who received targeted therapy first, those patients who received chemotherapy followed by targeted therapy presented longer time intervals to transformation (36 vs. 22 months). Genetic testing after transformation showed that eight patients still maintained the original epidermal growth factor receptor (EGFR) mutation types. The median progression-free survival (PFS) after transformation was 5 months, and the median survival time after transformation was 10 months in seven patients who died. Conclusions: Lung adenocarcinomas, once transformed to SCLC, progress rapidly and lead to poorer prognosis. After transformation, most of the patients maintain the original EGFR mutation types.