question: PURPOSE: Neuroendocrine neoplasia (NEN) of the thymus is a very rare entity with poor prognosis. No study based standard treatment is established. Usually therapy protocols for bronchopulmonary carcinoids are used. So far no data exist on the effect of mTOR-inhibitors. We describe our long term experience with everolimus and give a thorough review of the therapeutic strategies used so far. PATIENTS AND METHODS: 4 patients (mean age 46 years, range 37-55) with progressing thymic NEN (two well differentiated atypical carcinoids and two atypical carcinoids with large cell characteristics) were treated with everolimus 10 mg/d after failure of at least one previous medical therapy. Everolimus was applied after a mean interval of 32.4 months (range 5 - 56) after first diagnosis. The follow up included clinical examination, imaging, and chromogranin A testing in 3 or 6 monthly intervals. RESULTS: We observed stable disease for a mean of 20.8 months. Both patients with large cell characteristics thymic NEN (Ki-67 of 20 %) had rapid progress after 7 and 10 months and had more previous therapies (3 and 6) than the patients with well differentiated thymic NEN (Ki-67 5 % and 10 %, progress after 24 and 42 months, 1 and 2 previous therapies). No severe side effects occurred. In 3 out of 4 patients everolimus led to stable disease for the longest, compared to the other non surgical therapies used. CONCLUSION: Comparing the sparse data available everolimus is a promising treatment for thymic NEN at least in second line therapy. A low Ki-67 index was associated with a better outcome. This article is protected by copyright. All rights reserved.