This study assessed psychological distress and psychiatric disorder in high-risk women enrolled in a hereditary breast and ovarian cancer registry, and it evaluated the concordance between self-report data and interview-based psychiatric diagnosis. A sample of 464 women completed the Hopkins Symptom Checklist-25 and were interviewed using modules of the Structured Clinical Interview for DSM-IV. Level of psychological distress and the prevalence of psychiatric disorder were low and in the range that would be expected for a sample of community-residing women. Screening proved inefficient: Less than 10% of distressed women met criteria for a clinical disorder. High-risk women seeking genetic testing in research settings may not require extensive psychological screening and diagnostic assessment. Caution is expressed about possible self-selection biases in women enrolled in hereditary cancer registries.