AbstractBackgroundPersons with hereditary cancer syndromes (carriers) have a higher risk of developing cancer early. They are confronted with decisions regarding prophylactic surgeries, communication within their families, and childbearing. The present study aims to assess distress, anxiety, and depression in adult carriers and identify risk groups and predictors; clinicians can use to screen for particularly distressed persons.MethodsN= 223 participants (n =200 women,n =23 men) with different hereditary cancer syndromes affected and unaffected by cancer answered questionnaires measuring their distress, anxiety, and depression levels. The sample was compared to the general population using one‐samplet‐tests. Then= 200 women with (n =111) and without cancer (n =89) were then compared and predictors for increased levels of anxiety and depression were identified using stepwise linear regression analyses.Results66% reported clinical relevant distress, 47% reported clinical relevant anxiety, and 37% reported clinical relevant depression. Compared to the general population, carriers experienced increased distress, anxiety, and depression. Additionally, women with cancer suffered from more depressive symptoms than those without cancer. Past psychotherapy for a mental disorder and high distress were identified as predictors for increased anxiety and depression in female carriers.ConclusionsThe results suggest that the psychosocial consequences of hereditary cancer syndromes are serious. Clinicians could regularly screen carriers regarding anxiety and depression. TheNCCN Distress Thermometercan be combined with questions about past psychotherapy to identify especially vulnerable persons. Further studies are needed to develop psychosocial interventions.