Flow cytometric analysis of DNA content and ras p21 expression were studied in paraffin-embedded normal ovary (NO, n = 10), serous cystadenoma (SA, n = 11), serous tumors of low malignant potential (LMP, n = 13), and papillary serous cystadenocarcinoma (SCa, n = 7). Tissue for DNA analysis was processed via a modified Hedley technique; a separate aliquot of the same sample was stained with a monoclonal antibody directed to oncoprotein ras p21 (clone Y13259). NO (10/10) and SA (11/11) demonstrated diploid DNA stemlines; 4/12 LMP and 5/7 SCa were aneuploid. S-phase fraction varied with significant differences (p less than 0.001) for SA (mean = 4.4%), LMP (mean = 9.0%), and SCa (mean = 12.7%). When all cases were evaluated, p21 expression was relatively lower in NO and SA (mean = 4.2%) in contrast to LMP and SCa (mean = 13.0% and 8.1%). Diploid cases were examined separately, and lesions with high p21 expression were associated with a diagnosis of LMP/SCa (p less than 0.001), whereas diploid tissues with low p21 expression were associated with a nonmalignant diagnosis (NO/SA). This study suggests that aneuploidy or diploidy with high p21 expression (greater than 10%) may be associated with LMP or frankly malignant ovarian tumors.