The present study describes giant-cell tumor of bone (GCToB) with lymph node involvement in a 5-year-old crossbred cat. The animal was referred to the surgery clinic with progressive subcutaneous swelling in the left proximal femoral region, severe lameness, constipation, and dysuria. A moderately firm, subcutaneous, palpable mass, 9 cm in diameter, was observed, and biopsy samples were taken. Histopathologically, the mass was constituted by ovoid-shaped mononuclear cells intermixed with many multinucleated giant cells (MGC). Immunohistochemically, the giant cells were positively stained with antivimentin, and the same cells were negative for antidesmin and anti-S100 staining. Tartrate-resistant acid phosphatase (TRAP) activity in tumor cells was evaluated and the tumor was diagnosed as malignant GCToB; the cat was euthanized. Macroscopically, while the regional lymph nodes were intact, giant cells were found in the left popliteal lymph node during microscopy. Although a few cases of GCToB have been reported in cats, the case herein displays, for the first time, evidence of lymph node involvement during the process of metastasis.