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Rationale: Tenosynovial giant cell tumor (TGCT) is a neoplastic, inflammatory disease with a benign but aggressive course that often presents as localized (TGCT-L) and diffuse (TGCT-D) forms based on the growth pattern and clinical behavior. For TGCT-L, simple excision of the diseased synovial tissue is the preferred treatment option, while for TGCT-D, adequate synovectomy is usually tricky but is essential. However, approximately 44% of TGCT-D cases will relapse after surgery alone. Thus, the optimal treatment strategy in patients with TGCT-D is evolving, and standalone surgical resection can no longer be regarded as the only treatment. The previous studies have shown that postoperative adjuvant radiotherapy can reduce recurrence in TGCT, especially in patients with incomplete synovectomy. Patient concerns: In the first case, a 54-year-old male presented with recurrent pain and swelling of the right knee with a protracted disease course (≥10 years). The other patient is a 64-year-old male who developed swelling, pain, abnormal bending, and limited movement of the left knee without obvious inducement. Diagnoses: Clinical and imaging examinations can provide a definitive diagnosis, and pathology is the gold standard. TGCT-D was confirmed by postoperative pathology. After the operation, the patients underwent an MRI re-examination and showed that the lesions of the knee were not completely resected. Interventions: Arthroscopic synovectomy was performed on the patients, and postoperative pathology was confirmed as TGCT-D. Because of incomplete synovectomy, the 2 cases received image-guided, intensity-modulated radiotherapy (IG-IMRT) after the operation. Outcomes: The follow-up time was 1 year, no evidence of disease progression was found in MRI. No obvious adverse effects associated with radiotherapy were detected during the follow-up period. Lessons: These cases and reviews illustrate the necessity of radiotherapy for TGCT-D and that IG-IMRT is a safe and effective method for treating TGCT-D of the knee.