Chemotherapy has been the first-choice treatment for small-cell esophageal cancer (SCEC), etoposide plus cisplatin or carboplatin (EP/CP) is the most commonly recommended chemotherapeutical strategy. However, the choice of chemotherapy in treating SCEC has not been validated by studies of large cohorts of cases because of the rarity of the malignancy, and the efficacy superiority of EP/CP over other chemotherapy combinations has not been confirmed. The present case series analysis was conducted to address the above issues. Reported studies of SCEC patients were retrieved. Case series with more than five patients were enrolled. Eight patients treated in our institute were also included as another case series. Data pertaining to clinical stages, treatment regimens, and survival time were collected and analyzed. Altogether, 19 SCEC case series were enrolled, including 164 male and 61 female patients with a median age of 63.5 years. The follow-up time ranged from 0.1 to 221 months (median 12.3 months). The median survival time (MST) was 19 months for limited disease (LD) patients (124 cases) and 9 months for extensive disease (ED) patients (88 cases) (P<0.001). For LD patients, MST was obviously prolonged by chemotherapeutical regimens (20 vs. 10 months, P<0.01), whereas this superiority was not proved in ED patients (10 vs. 10 months, P>0.05). EP/CP did not result in significantly longer MST, compared with that of the cases treated by other chemotherapy combinations (P>0.05, for either LD or ED cases). Chemotherapy prolongs the survival time of the LD SCEC patients, which indicates that chemotherapeutical treatment is effective for SCEC. EP/CP, as commonly recommended multidrug chemotherapy regimen, is not superior to other chemotherapy combinations.