Giant cell tumor of the tendon sheath (GCTTS) is a benign tumor with a high recurrence rate of up to 50%. The lesion may appear anywhere in the synovium; the nature of this tumor is still controversial, however recent data shows that tenosynovial giant cell tumors (TGCTs) could be clonal neoplastic tumors. Most lesions of GCTTS produce one or more discrete nodules, while the radiological features can include soft-tissue masses with or without bone destruction. In an effort to advance in the understanding of GCTTS pathogenesis, we decided broadly investigate the immunophenotypic profile, of a TGCT in a 69-year-old female patient.