Objective: Desmoid tumors (DTs) are clonal fibroblastic/ myofibroblastic proliferations. Although histologically benign, desmoids are locally invasive and often have an unpredictable clinical course. DTs are infrequent lesions, but they have a high incidence in patients with familial adenomatous polyposis (FAP). The treatment of DTs needs to be individualized. Method: To explore the molecular bases of potential pharmacologic targets in DTs we evaluated the immunohistochemical expression of steroid hormone receptors (ERa, ERb, PR) and COX-2 protein in sporadic (n=6) and FAPassociated desmoid tumors (n=9) together with GI adenomas of FAP patients (n=5). Results: Nuclear ERb expression was found in 14/15 DTs. All adenoma samples showed nuclear ERb positivity, which was weaker than in the surrounding normal epithelial cell. ERa and PR expression were lacking in all samples. COX-2 was found in 14/15 DTs. Adenomatous polyps showed intense COX-2 expression compared to surrounding normal mucosa. Conclusion: High incidence of ERb positivity in DTs supports the usage of hormonal therapy in these lesions. Open question is the effect of anti-estrogen therapy in DT patients with adenomatous polyps, as in adenomas estrogen seems to have preventive potential. COX-2 expression suggests the benefit of anti-inflammatory treatment in DTs adenomatous polyps. Supported by ITMS: 26240220052.