A 67-year-old female patient was admitted to the hospital for one week after touching solitary painless mass in the left popliteal fossa. Her past medical history had been uneventful, and her family history exhibited no malignancies. Physical examination: A round soft tissue nodule was touched behind the left knee joint, approximately 3.0 cm in size, with mild tenderness and mobility. Physical examinations of the chest and abdomen were unremarkable. Laboratory examination: uric acid 488.0 μmol/L (normal reference value 255 ~ 357 μmol/L), other laboratory examinations showed no abnormalities. Imaging examination: Ultrasound showed a solid hypoechoic mass of 3.2 cm × 2.4 cm in the left popliteal fossa, with blood flow visible, it was hard to determine whether the lesions are benign or malignant. An unenhanced MRI scan showed multiple soft-tissue masses of different sizes in the left popliteal muscle space. The T1 weighted image showed hypointense to isointense, the fat-suppressed T2 weighted images showed subtle hypersignal intermingled with linear of hypointense, and the larger lesion was an oval shape, lesion size was 3.2 cm × 1.9 cm × 2.1 cm, smooth edges, and displayed homogeneous contrast enhancement after administration of gadolinium; two small lesions with similar signal and enhancement degree can be seen in the muscle space above the lesion. Preoperative biopsy revealed a lymphoid tumor of unknown dignity, routine histopathological examination should be performed. Surgical and pathological findings: Complete surgical resection was performed and three soft nodules having a maximum diameter of 3.2 cm were removed, presented as a sharply demarcated mass lesion. The popliteal arteries and veins were intact. Postoperative pathology: Grossly, the resected tumor specimen displayed a sharply demarcated and medium hardness mass lesion with a gray-red cut surface. Microscopically, the lymph node structure was basically present, the envelope was intact, the lymphatic follicles in the lymph nodes were hyperplastic, the small blood vessels showed varying degrees of hyperplasia, and a large number of patchy, dense plasma cell infiltrates were seen between the follicles. Immunohistochemical staining: CD3 interfollicular areas ( +), CD43 interfollicular areas ( +), Pax-5 follicular areas ( +), germinal center (Bcl-2-, Ki-67 > 70%), extra-germinal center (Bcl-2 +, Ki-67 about 5%), CD10 germinal center ( +), CD34 vascular ( +), CD21 FDC ( +), plasma cells. CD138 ( +), λ ( +) > κ ( +)。The morphological examination was performed using Carl Zeiss Axio Lab.A1. The slides were scanned by using the KF-PRO-005 digital pathology scanner (KFBIO85 company, Ningbo City, China). Pathological diagnosis: (Multiple left popliteal fossa) Castleman's disease, plasmacytic type. Postoperative recovery was good and discharged. The patient documented in this report was doing well on 12-month follow-up.