The rare incidence of small cell carcinoma of the esophagus (SCCE) makes prospective studies difficult to conduct, the efficacy of existing standard treatment regimens for SCCE is therefore highly controversial. This study aimed to explore differences in the efficacy of three different treatment regimens [upfront surgery, neoadjuvant chemotherapy (NCT), and chemoradiotherapy (CRT)] in patients with limited-stage SCCE (LS-SCCE).In total, 483 patients with LS-SCCE were screened from five centers from June 2001 to June 2020, and 128 patients with LS-SCCE were screened from the Surveillance, Epidemiology, and End Results (SEER) database. A survival analysis of the patients who underwent upfront surgery, NCT, and CRT was performed. The primary endpoint was overall survival (OS).Treatment approaches for LS-SCCE differ between China and America. The data from the SEER database showed that aggressive treatment resulted in a significant survival benefit for patients [median OS (mOS), 16.0 vs. 1.0 months]. However, no significant survival difference was observed between the surgical and non-surgical treatments [China: hazard ratio (HR), 0.820; 95% confidence interval (CI): 0.618-1.088, P=0.17; SEER: HR, 0.717; 95% CI: 0.440-1.169, P=0.18]. CRT significantly improved the survival time of the patients aged >60 years (mOS, 20.9 vs. 36.0 months, P=0.007). NCT significantly prolonged the survival time of the patients who underwent esophagectomy (HR, 0.753; 95% CI: 0.569-0.995, P=0.046).This study suggests that NCT provided a better survival benefit for patients with LS-SCCE than upfront surgery, LS-SCCE patients aged >60 years receiving CRT had survival benefit compared to those undergoing surgery.2024 AME Publishing Company. All rights reserved.