Ovarian tumors of low malignant potential ("borderline tumors") have been proposed variably to represent a distinctive type of malignancy, precursors of frank ovarian malignancy, or a nonmalignant process. We analyzed 81 malignant and 39 borderline ovarian tumors for p53 immunoreactivity and alterations in codon 12 of Ki-RAS in order to correlate these alterations with tumor and cell type. Diffuse p53 immunoreactivity was significantly more prevalent among malignant (36 of 81, 44%) than among borderline (3 of 39, 8%) tumors and was particularly prevalent among serous invasive carcinomas (16 of 26, 62%). Conversely, mutations in codon 12 of Ki-RAS were significantly more prevalent in borderline (16 of 39, 41%) than in malignant (9 of 81, 11%) ovarian tumors and were most prevalent among mucinous tumors. This preliminary molecular analysis suggests that serous borderline tumors have some molecular features usually associated with malignancy but are unlikely to represent a precursor of invasive serous carcinoma. In contrast, mucinous borderline tumors may represent a precursor or variant of mucinous carcinoma of the ovary.