Objective: The European Registry on Cushing's syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushing's syndrome (CS). Design and methods: Baseline data on 481 CS patients (390 females, 91 males; mean age (+/- S.D.): 44 +/- 14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%). Results: Proportion of men in the ECT-CS group was higher than in the other groups (P < 0.05). The ADR-CS group was older than the PIT-CS (P < 0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT-CS was higher than in the other groups (P < 0.05 and P < 0.01 respectively). PIT-CS had more skin alterations, menstrual irregularities and hirsutism than ADR-CS (P < 0.01). Reduced libido was more prevalent in men than women (P < 0.01). Prevalence of spine osteoporosis was higher in men than women (P < 0.05), and males had more vertebral and rib fractures than females (52 vs 18% for vertebrae; P < 0.001 and 34 vs 23% for ribs; P < 0.05). ECT-CS consulted a diabetologist more frequently than ADR-CS (P < 0.05), while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS (P < 0.05). Overall, weight gain was more common in women than men (P < 0.01). CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups. Conclusions: The ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology.