The current biomarker for ovarian cancer, CA125, lacks the sensitivity and specificity required to detect early stage ovarian cancers. Since several Kallikreins (KLKs) are up regulated in ovarian cancer, they represent a potential pool of biomarkers for ovarian cancer. The purpose of this study is to determine if elevated expression levels of Muc16 (CA125 gene), KLK6 and KLK13 represent a more sensitive test for detection of early stage ovarian cancer than Muc16 alone. Using quantitative real-time PCR, 106 sporadic ovarian tumors and 8 normal ovaries were evaluated for mRNA expression. Analysis for increased expression levels, above controls, of either KLK6, KLK13 or Muc16 improved overall sensitivity to 93%, from 82% for Muc16 alone. Likewise, the negative predictive value increased from 27% to 50% (Muc16 alone compared to combined). With early stage cancers (n=32), both sensitivity increased 50-56% (individually) to 72% (combined), and negative predictive value increased (30% Muc16 to 58% combined). These results show a combined panel of KLK6, KLK13, and Muc16, is a more sensitive test to detect early stage ovarian cancer than Muc16 alone, indicating assaying for several kallikrein-related peptidases, in addition to CA125, could provide a significant advantage to detect ovarian cancer in the early stages.