Background: Castleman’s disease (CD) is a rare, benign lymphoproliferative disorder that can involve single lymph node stations or can be systemic. Unicentric CD in patients with microcytic anemia is rarely described in the English literature. Case Report: We describe the case of a 19-year-old Chinese woman with hyaline vascular type of unicentric CD presenting as severe non-iron deficiency microcytic anemia. We report the clinical course from the initial presentation to diagnosis and surgical cure, and discuss the most up-to-date information on CD. Conclusions: CD should be included in the differential diagnosis of microcytic anemia. Imaging tools and pathological studies should be considered in order to make a more accurate diagnosis and to avoid the use of ineffective treatments.