Early detection of cancer remains a significant challenge. Existing liquid biopsy approaches to detect early-stage cancer show promise but suffer significant limitations including the abundance and stability of the analyte, large sample requirements, and insufficient specificity to distinguish biomarkers as originating from benign or cancerous cells. Extracellular vesicles (EVs) from cancer cells exhibit both stability and abundance in human biofluids which makes them an attractive target for early-cancer detection. Measurement of multiple, colocalized cancer-associated biomarkers on single EVs may improve upon existing methods for the non-invasive detection of cancer. To demonstrate this, we developed Mercy Halo(TM), an immunoassay designed to capture and detect cancer-specific biomarkers on the surface of EVs derived from cancer cells. Our platform shows promise for the sensitive and specific detection of early-stage ovarian tumors in human plasma, outperforming a single biomarker (CA125), for the detection of stage I and II high-grade serous ovarian cancer (HGSOC).