Ovarian serous tumors of borderline malignancy frequently show morphologically benign and borderline areas within the same tumor. This study was undertaken to determine if these two morphologically disparate areas differ in their proliferative activity and p53 expression. Formalin-fixed, paraffin-embedded archival tissue from 17 ovarian serous borderline tumors with morphologically benign and borderline areas were immunostained with monoclonal antibodies against p53 and MIB1. The percentage of positive cells was determined by counting 100 consecutive cells for each stain in the most intensely stained areas in morphologically benign and borderline portions of these tumors. There was a significantly increased proliferation (MIB1 expression) in borderline areas compared with benign areas (37.05 +/- 15.3 versus 12.88 +/- 6.7, p = 0.0001). More than 30% of cells were positive for MIB1 in 13/17 borderline areas compared with none of the 17 benign areas (p < 0.0001). The expression of p53 was also higher in borderline areas compared with benign areas (7.12 +/- 8.8 versus 2.94 +/- 4.46, p = 0.0078). More than 10% of cells were p53 positive in 5/17 borderline areas compared with 1/17 benign areas (p = 0.08). However, there was no significant correlation between p53 expression and MIB1 expression in either the benign or borderline areas (p = 0.4 and 0.2, respectively). In summary, morphologically borderline areas show significantly higher p53 expression and proliferation compared with morphologically benign areas in ovarian serous borderline tumors. Alterations of p53 may play a pathogenetic role in some ovarian serous borderline tumors. The lack of correlation between p53 expression and MIB1 expression, however, suggests involvement of other factors, in addition to p53, in determining the proliferative rate of ovarian serous borderline tumors.