Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a complex vascular lesion recently described. We present a case of SANT occurring in a 49-year-old woman who was treated for choroid melanoma. The computed tomography abdominal scan revealed an asymptomatic mass in the spleen. Splenectomy was performed due to the risk of metastasis from the melanoma. The histopathologic examination revealed an angiomatoid lesion composed of three types of vessels recapitulating the normal composition of the red pulp of the spleen. In this report, we discuss the pathology of this lesion and the differential diagnosis of SANT with other lesions such as hemangiomas, hamartomas and inflammatory pseudotumors.