Objective To study the clinicopathologic features, immunophenotypes and differential diagnosis of myxoinflammatory fibroblastic sarcoma (MIFS). Methods The clinical and pathologic features of 6 cases of MIFS were analyzed. lmmunohistochemical study was performed using the standard EnVision method. Results There were altogether 2 adult males and 4 adult females ( median age =47 years and mean age = 50 years). Three cases were located in the lower extremities, 2 in the upper limbs and 1 in the axillary region. Common presentation included slowly growing mass or swelling in the extremities, accompanied by mild pain or tenderness. Grossly, the tumor appeared multinodular and ranged from 2. 5 cm to 4. 6 cm in diameter ( mean = 3.4 cm). Microscopically, there was a dense inflannatory infiltrate merging with hyaline and myxoid zones in various proportions. Spindle-shaped tumor cells were seen admixed with large atypical cells which distributed singly or in small clusters, amongst an inflammatory, hyaline or a myxoid background. These atypical cells had large nuclei and prominent nucleoli, resembling virocytes, Reed-Sternberg cells or ganglion cells. Mitotic figures were rarely identified. Extracellular mucin associated with scattered monovacuolated or multivacuolated lipeblast-like cells was noted. Immunohistochemically, these bizarre cells were consistently positive for vimentin, but negative for a panel of antibodies including LCA,CD15, CD30, CD34, CD68, S-100, HMB45, AE1/AE3, smooth muscle actin and desmin. Follow-upresult was available in 4 cases; and 2 of them showed local recurrence after an incomplete excision. There was no evidence of distant metastasis. Conclusions MISF is a low-grade sarcoma of fibroblastic differentiation. Awareness of the clinical and pathologic characteristics is helpful in arriving at the correct diagnosis and distinction from benign inflammatory fibromyxoid lesions.