Inflammatory fibrosarcoma (commonly referred to as inflammatory myofibroblastic tumor) has become increasingly recognized as part of a spectrum of inflammatory myofibroblastic proliferations. It is a potentially locally aggressive myofibroblastic tumor that occurs predominantly in the mesentery of children and young adults. No reliable morphological parameters have been identified that predict prognosis. We evaluated the ultrastructural and immunophenotypic features of 16 cases of inflammatory fibrosarcoma and studied Ki67 (MIB1), PCNA, bcl-2, and p53 in an effort to identify prognostic markers. p53 was not detected immunohistochemically in any case. None of the markers were found to correlate with local recurrences, metastases, or tumor deaths. Low proliferative activity (Ki67 < 10%) was seen in all cases. A characteristic immunophenotype was reconfirmed in which lesional myofibroblasts stained for vimentin, alpha-smooth muscle actin, cytokeratins, and rarely desmin. Ultrastructural studies of seven cases confirmed the presence of a fibroblastic-myofibroblastic spectrum. Because inflammatory myofibroblastic tumor-inflammatory fibrosarcoma is associated with systemic symptoms, polymerase chain reaction studies for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were performed in 12 cases. Evaluable results in nine cases did not show evidence of either virus. The results of this study indicate that inflammatory fibrosarcoma has a low proliferative activity, which is in keeping with the impression that this is a low-grade sarcoma; that myofibroblasts can participate in true neoplasia; and that EBV and CMV do not play a role in the pathogenesis of inflammatory fibrosarcoma. The variable phenotype of the myofibroblast and its role in reactive and neoplastic processes are discussed. A perspective on the position of inflammatory fibrosarcoma in the spectrum of inflammatory myofibroblastic tumors is also given in light of the current study and the literature.