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Thrombotic manifestations are common in cancer patients and increase morbidity and mortality. They can affect large or small, venous or arterial vessels. Thrombosis of large arteries and veins is much more studied than that of small vessels. Nevertheless, thrombotic micro-angiopathies - a group of disorders characterized by microvascular thrombosis, thrombocytopenia, and ischemic organ failure - represent a severe and often fatal complication of cancer natural history, as their diagnosis is not always prompt and easy, and treatment controversial or ineffective. Herein, we report a case of sub-acute/acute cor pulmonale in a patient with advanced gastric cancer, treated with mitomycin C, as a good model for differential diagnosis of cancer-related thrombotic micro-angiopathies.