Myofibroblastoma (MF) is an uncommon, usually benign, mesenchymal tumor infrequently described in soft tissues. We report here on the clinicopathologic findings of a soft tissue MF (STMF) presenting in the neck of a 90-year-old man as a slowly growing and non-painful nodule, 4 cm in greatest diameter. Histology revealed a circumscribed lesion constituted of monomorphous bipolar spindle cells arranged in swirling fascicles with intervening broad bands of hyalinized collagen and well formed "amianthoid" fibers. Immunohistochemistry showed the spindle cells to be immunoreactive for vimentin, smooth muscle actin and muscle specific actin and, focally, for desmin; immunostaining for cytokeratin, epithelial membrane antigen, S-100 protein, factor VIII-related antigen, and CD34 was negative. Based on the present case and on those previously reported in the literature, STMF is characterized by: 1) exclusive incidence in the male sex; 2) variable immunoreactivity of the neoplastic cells for desmin, probably reflecting an origin from a peculiar subset of myofibroblasts, or, alternatively, a further myoid differentiation; 3) variable abundance of (hyalinized) collagen; 4) presence of amianthoid fibers. The combination of desmin immunoreactivity, frequently observed in MF of the breast, and amianthoid fibers, the main feature of MF of the lymph nodes, has never been observed in soft tissue MF. It is important to recognize STMF as a specific clinicopathologic entity to avoid confusion with other types of spindle cell proliferation and to differentiate it from other types of myofibromatosis.