Abstract: Primary small cell carcinoma of the esophagus (PSCCE) is a high-grade neuroendocrine tumor originating from the esophagus, characterized by a short doubling time, high growth score, and early metastasis. Due to the extremely low incidence of PSCCE, it is difficult to perform randomized controlled studies with large sample sizes. Previous studies on PSCCE have largely been based on case reports. Additionally, there is no uniform standard for the selection of a treatment regimen for this disease. However, in recent years, a greater number of studies have been conducted on PSCCE. Meanwhile, the arrival of the era of precision medicine has contributed to more studies focusing on the molecular mechanisms of PSCCE. This review focuses on the recent research progress in PSCCE with respect to investigating molecular mechanisms, treatment, and other aspects of the disease to provide further insight into new possibilities for the future diagnosis and treatment of PSCCE.