Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas of adulthood. Although it is usually intramuscular and pseudocapsulated, we have recently observed MFHs with extremely infiltrative growth margins, which are predominantly located in the subcutis. These lesions are often associated with incomplete primary surgical excision, the subsequent need for additional surgery or adjuvant therapy, and an increased risk for local recurrence. To further analyze the growth pattern and clinical implication of the subcutaneous infiltrative MFHs, we reviewed a series of 24 subcutis and 21 intramuscular MFHs of the extremities. Morphologically, we defined "infiltrative" as tumor extension along normal tissue planes for a minimum measurable distance of 2 mm from the edge of the main mass. Radiographic findings were correlated with pathologic findings. Of the 24 subcutis MFHs, 83% showed an infiltrative growth pattern, involving 5% to 90% (mean, 51%) of the evaluable margin. Fifty percent of patients with subcutaneous MFH had both an infiltrative growth pattern and positive surgical resection margin on initial resection. Only 25% noninfiltrative subcutaneous MFHs had a positive initial surgical resection margin. Of the 21 intramuscular MFHs, only 5 (24%) had an infiltrative growth pattern that involved 5% to 90% (mean, 40%) of the evaluable margin. One of the five tumors had 90% margin infiltration with multiple positive surgical resection margins. Of 16 noninfiltrative intramuscular MFHs, 3 (19%) had positive resection margins. Magnetic resonance imaging (MRI) and/or computed tomography (CT) scan correctly identified the growth pattern in 87% of subcutaneous and 88% of intramuscular MFHs. Patient follow-up evaluation showed that four (17%) patients with subcutaneous MFHs had resection-proven recurrences, 6 to 57 months after diagnosis. All four of these tumors had infiltrative growth patterns and positive margins on the original surgical resection. There were no local recurrences of the intramuscular MFHs. Two patients of 20 in the infiltrative subcutaneous MFH group and two patients of four in the well-circumscribed subcutaneous MFH group had biopsy-proven metastases, which developed within 5 years after diagnosis. Six patients had metastases in the intramuscular MFH group. A group of MFHs, predominantly subcutaneous, have an extremely infiltrative growth pattern. This growth pattern, documented by radiographic methods and/or light microscopic examination of biopsy specimens, should indicate that a wider margin on initial resection is necessary to entirely excise the lesion. The presence or absence of an infiltrative growth pattern is not predictive of the tumor's metastatic potential.