Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related complication with rapid progression. Although the underlying molecular mechanisms of PTTM remain unclear, platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) may play important roles in the pathogenesis of PTTM. We herein report a case of PTTM that was diagnosed antemortem by pathology using pulmonary wedge aspiration. The patient was treated with a combination therapy of imatinib (PDGF receptor antagonist), bevacizumab (VEGF receptor inhibitor), S-1, and cisplatin. These findings suggest that molecular-target drugs are effective for the treatment of PTTM.