Dermatofibromas (DF) are common, benign skin tumors composed predominantly of cells having elongated nuclei and very scant cytoplasm (i.e., fibroblasts) and capillaries in a collagenous stroma. Some authors distinguish DF from benign fibrous histiocytomas (BFH), which are composed of cells with round to oval nuclei and abundant cytoplasm (i.e., histiocytes). In general, this group of tumors expresses factor XIIIa but not the antigen recognized by MAC 387. However, immunohistochemical differences specifically between DF and BFH have not been reported. We have studied the immunophenotype of 23 lesions having morphologic features predominantly either of DF (17 cases) or BFH (6 cases) using antibodies against desmin (muscle marker), alpha-smooth-muscle actin (muscle and myofibroblast marker), CD68 and HAM56 antigen (markers commonly expressed by macrophages, so called "histiocytic" markers), CD34 (a marker present in hematopoietic, vascular, and occasional dermal dendritic cells), and factor XIIIa (a transglutaminase present in many cells including dermal dendrocytes). Many spindle-shaped cells expressed alpha-smooth-muscle actin while many large, round cells expressed the histiocytic markers. However, most lesions expressed at least focally both alpha-smooth-muscle actin and "histiocytic" markers. Thus a clear-cut distinction between DF and BFH could not be made based on immunophenotype alone. Additionally, the prominent alpha-smooth-muscle actin immunoreactivity and desmin non-reactivity suggests myofibroblastic differentiation in the spindle-cell regions of these tumors, and indicates that expression of alpha-smooth-muscle actin cannot be used as definitive proof of muscle differentiation in spindle-cell tumors. We conclude that DF and BFH are not discrete entities, but represent polar expressions of one nosologic entity exhibiting both myofibroblastic and "histiocytic" differentiation.