An observational study of the performance of serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm, reveals the sensitivity of this approach in women with a high risk of ovarian cancer. In the study cohort consisting of 4,348 women, 19 were diagnosed with ovarian cancer, with a modelled sensitivity of 94%. Six of these diagnoses were of occult disease on follow-up transvaginal sonography, as used in women with a >10% lifetime risk detected during initial screening. 18 of the 19 women diagnosed within 1 year of commencing screening had no residual disease, highlighting the value of early diagnosis.