To our knowledge, the occlusion of arteries and platelet hyperaggregation have not been reported in patients with malignant mesothelioma. However, venous thromboembolism, especially in the pulmonary vasculature in association with thrombocytosis and hyperfibrinogenemia, are commonly noticed in this disorder. Furthermore, we detected enhanced platelet aggregation in a case of malignant peritoneal mesothelioma with internal carotid artery occlusion in whom there were postsplenectomy thrombocytosis and hyperfibrinogenemia. The possible mechanisms of ICA occlusion in this patient, including the role of MPM and postsplenectomy state, thrombocytosis, platelet functional changes, and other factors were investigated and discussed.