The level of serum amyloid A, a protein previously found to behave as an acute-phase reactant, was measured by a radioimmunoassay in 621 patients with various neoplastic diseases free of inflammatory processes. In all but eight of the 289 patients with solid tumors with distant metastases, in all patients with myelocytic leukemia with high leukocyte counts, and in all patients with advanced lymphoma, the serum amyloid A level was above 400 ng/mL. It was below this value in all tested patients with lymphocytic leukemia and in 250 of 270 patients with solid malignant tumors with localized or regional disease. Among the 20 patients from this latter group with levels higher than 400 ng/mL, 16 developed distant metastases within 214 days from the initial measurement. The serum amyloid A level decreased significantly in patients with lymphoma and those with metastatic solid tumors who responded to chemotherapy. Thus the level of serum amyloid A can be used as a biochemical marker that discriminates between disseminated and localized or regional disease, and monitors the response to therapy.