Epithelioid hemangioendothelioma of soft tissues (EHE) represents a distinct entity with an unpredictable clinical course. We analyzed the clinicopathologic and immunohistochemical features in a series of 30 patients. Patient age range was 16-74 years (median 50); 18 of 30 patients were female. Eight tumors arose in the lower and two in the upper extremities, seven on the trunk, five each in the head/neck and anogenital regions, two in the mediastinum, and one in the abdomen. Seventeen neoplasms were located in deep soft tissues, nine were subcutaneous or perifascial, and four were dermal; size ranged from 0.4 to 10 cm; in 11 cases the tumor was >5 cm. Tumors with an infiltrative growth pattern were more common than entirely circumscribed lesions. The tumors were composed histologically of short strands, cords, or small clusters of epithelioid, round, to slightly spindled endothelial cells that formed at least focally, intracellular lumina and were set in a frequently myxohyaline stroma. Thirteen of 30 lesions showed angiocentric growth, which was occlusive in many cases. Immunohistochemically, all cases tested were positive for at least one endothelial marker (CD31, CD34, factor VIII, Ulex europaeus), six of 23 (26%) were positive for cytokeratin, and five of 11 (45%) were positive for alpha-smooth muscle actin. Median follow-up of 36 months (range 2-96) in 24 cases showed local recurrence in three cases and systemic metastases in five cases (21%); four patients (17%) died of tumor. Although more aggressive histologic features (striking nuclear atypia in eight cases, numerous spindled cells in 10, more than two mitoses per 10 high-power fields in nine, and small, more solid angiosarcomalike foci in four cases) tended to be related to poor clinical outcome, there was no clear correlation. Two metastasizing cases showed no histologically atypical features whatever. We suggest that EHE of soft tissue is better regarded as a fully malignant, rather than borderline, vascular neoplasm, albeit the prognosis is better than in conventional angiosarcoma.