Patterns of tumor spread were studied by examining clinicopathologic and postmortem data on 274 tumor-related deaths from patients in IRS-I and IRS-II. The activity of the primary lesion and presence or absence of distant metastases at death were related to the histologic subtype and anatomic site of origin, individually and/or in combination. The alveolar subtype had the highest proportion of distant metastases and the lowest occurrence of local progression alone from the primary site. More distant metastases were observed among the patients with extremity primary, and the frequency increased significantly with the alveolar histologic subtype. Parameningeal tumors, irrespective of their histologic subtypes, showed a high incidence of direct extension from the primary lesion especially into the CNS. The lung was the most common site of metastasis at death, followed by the regional lymph node, bone, liver, and brain. Regional node involvement was observed more commonly in patients with lower extremity primary and alveolar subtype.