Ewing's sarcoma (ES) is an aggressive cancer in young adults. Primary ES occurring in the chest with pleural effusion is even rarer. We report the case of a 15-year-old girl who presented with intermittent chest pain occurring for more than 2 months and cough and wheezing for 10 days. Radiological imaging showed a large soft tissue mass with multiple small vessel shadows near the left mediastinum and bloody pleural effusion in the left thorax. ES was diagnosed by positive immunostaining for CD99, FLI-1, and NKX2 combined with fluorescence in situ hybridization detection of the EWSR1 gene arrangement. With chemotherapy, lung computed tomography revealed that the tumor had become much smaller, and the fluid was absorbed. We report a case of extraskeletal Ewing's sarcoma (EES) in the mediastinum with pleural effusion, which is unusual and challenging. EES is a highly malignant tumor with a poor prognosis. Early diagnosis and treatment can improve the survival rate of patients.