The patient was a 7-year-old boy admitted with facial edema. Ultrasound indicated moderate pericardial effusion and pleural effusion. Contrast-enhanced chest computed tomography showed indistinct mediastinal structures with mild-to-moderate enhancement, suggestive of a mediastinal space-occupying lesion. Further evaluation with whole-body PET-CT, pathological biopsy of the mediastinal lesion, cytological examination of pleural and pericardial effusions, and immunohistochemistry led to the final diagnosis of isolated myeloid sarcoma. Pathological examination is the gold standard for clinical diagnosis; however, limited sampling sites can result in missed or incorrect diagnoses. Multiple and multi-site sampling should be undertaken according to the clinical context, combined with flow cytometry and immunohistochemistry to assist diagnosis and reduce missed diagnoses and misdiagnoses.