A 2.5-year-old, male, neutered cat presented with a 5-month history of progressive right hind limb lameness and an enlarged right popliteal lymph node. Radiographs revealed significant bony lysis of the tarsus and distal tibia, and fine-needle aspirate of the bone lesion and lymph node revealed a neoplastic population of cells with uncertain origin. Amputation was elected, and the mass was submitted for histology and cellular culture for better characterization. Histologic examination revealed a mixture of spindle-shaped cells and larger, round to polygonal cells. All cells were immunoreactive for vimentin, and only the larger polygonal cells were also positive for cytokeratin. All cells were negative for desmin, smooth muscle actin, cluster of differentiation (CD)3, CD18, CD79a, macrophage antibody (MAC)387, and glial fibrillary acidic protein. Cultured neoplastic cells failed to express CD18, and were not able to secrete the pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1 (IL-1)β, and IL-6 when stimulated by lipopolysaccharide, disproving that the cells originated from the macrophage or monocyte line. Ultrastructurally, neoplastic cells were characterized by abundant rough endoplasmic reticulum, interdigitating cellular processes, and membrane condensations. Based on location and cytologic, histologic, ultrastructural, and functional studies, this neoplasm was considered a synovial cell sarcoma.