In a retrospective study of 60 spindle-cell sarcomas of peripheral soft tissues, we evaluated the extent of immunostaining with antibodies against Ki-67, proliferating cell nuclear antigen, and p53 protein and flow-cytometric DNA ploidy, their relation to tumor location, depth, histologic type, size, mitotic rate, and extent of tumor necrosis, as well as their influence on survival. Although Ki-67-labeled nuclei were detected in only 41 tumors (68%) and their number varied from 1 to 50%, proliferating cell nuclear antigen immunoreactive nuclei were found in each tumor, with their number ranging from 20 to 99%. p53 Protein was found in 26 cases (43%), and its labeling ranged from 1 to 80%. Although Ki-67 labeling significantly correlated with mitotic rate, no correlation could be found between proliferating cell nuclear antigen or p53 labeling and any other variables studied. Thirty-eight percent of the tumors were diploid, and 64% were aneuploid. Factors that significantly reduced survival in univariate analysis were increasing size and depth of the tumor, the presence of necrosis, the National Cancer Institute grade, and a tetraploid/hypertetraploid DNA pattern. In multivariate analysis of 49 cases with complete information, only DNA ploidy pattern, tumor size, and tumor necrosis retained their independent prognostic significance.