Patients with metastatic Ewing's sarcoma of bone have a poor prognosis. A relation between clinical characteristics and presence of metastatic disease at diagnosis in patients with Ewing's sarcoma of bone was investigated. Data from 618 patients [136 (22%) with metastases at diagnosis] registered at the authors' institution between April 1972 and December 1997 were collected. The distribution of several clinical and hematologic parameters in patients with metastases and those without metastases was analyzed, and clinical risk factors of metastatic disease at presentation were analyzed by means of multivariate logistic regression analysis. All the variables significant at the univariate analysis (age, fever, site, volume, lactic dehydrogenase, anemia, and interval between onset of symptoms and diagnosis) were considered in the multivariate analysis. Pelvic location of the tumor, high level of lactic dehydrogenase, presence of fever, an interval between onset of symptoms and diagnosis less than 3 months, and age older than 12 years were found to be risk factors of clinically evident metastatic disease. In the subset of patients with no risk factors the rate of metastatic disease at presentation was only 4%; in case of contemporary presence of two factors it was 23%, although it was almost double (44%) if three or four factors were present. Only six patients were positive for five factors and all of them had metastases at presentation. The parameters identified are clinical markers of Ewing's sarcoma having a particularly aggressive metastatic behavior.