BACKGROUND: Mesenteric and duodenal leiomyosarcomas are very rare malignancies. Muscular metastases from leiomyosarcoma are even more rare. Surgery is the only chance of cure and should be attempted whenever possible. The relief of symptoms and the prevention of recurrences are ultimately the aims of surgery. We present a unique case of mesocolic and duodenal leiomyosarcoma with muscular metastases. CASE REPORT: A 61 years old woman was treated by radical resection including left nefrectomy and left hemicolectomy for a leiomyosarcoma of the left mesocolon. Three years after the first surgery a leiomyosarcoma of the duodenal wall was diagnosed. Following a careful evaluation that ruled out the presence of other secondary locations, she underwent pancreatoduodenectomy. Three months later she observed a small, mildly painful swelling in the left thigh, rapidly growing to a diameter of 4 cm over a month period. The MRI showed a low-signal intensity malignancy in T2-weighted images whereas the lesion was homogeneously enhanced by Gadolinium on T1-weighted imaging. The histological examination after excision confirmed the clinical suspicion of a metastasis from high grade leiomyosarcoma. Successively the patient underwent a palliative chemotherapy treatment with epirubicin and ifosfamide for three cycles. The patient experienced a progression of disease with multiple pulmonary and encephalic metastases five months later. CONCLUSION: Muscular metastases from leiomyosarcoma are occasionally described in the literature. The apparition of muscular metastases is considered a negative prognostic factor and shortly precedes massive distant diffusion of the malignancy. Denervation syndrome can be a risk factor for muscular metastases. To our knowledge, this is the first report of a skeletal-muscle metastasis following mesenteric and duodenal leiomyosarcoma.