The diagnosis and staging of soft-tissue tumors is a complex problem, and even the experienced pathologist sometimes finds it difficult to determine whether a particular lesion is benign or malignant and whether a sarcoma is high or low grade. However, this information is essential in planning treatment. Flow cytometric analysis of nuclear DNA is a method to determine the number of cells that are in the process of replicating or dividing (S or G2, or M phase), since these cells have abnormal concentrations of DNA (DNA aneuploidy). Previous studies from our laboratory have established the relative value of this technique as an adjunct in the staging of primary bone tumors. In the past four years, 146 soft-tissue lesions have been evaluated by flow cytometry, using propidium iodide staining of isolated cells that were obtained in the fresh state. The tumors were forty-two benign neoplasms, ten lesions of synovial origin, thirty desmoids (aggressive but not malignant), and sixty-four sarcomas ranging in grade from 1 to 3 on a 3-point scale. The over-all values for flow cytometry showed that a number of factors correlated well with the grade of the tumor, but the best correlations were with the mean concentration of DNA (a calculated average for concentrations of DNA for the various types of cells in the lesion), the total percentage of cells in S-phase plus the G2 and M-phases (called percentage of replicating and dividing cells), and the presence or absence of DNA aneuploidy.(ABSTRACT TRUNCATED AT 250 WORDS)