Background <p>Cabozantinib is a multi-kinase inhibitor that has been shown to be effective in the treatment of unresectable or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma that worsened after anticancer drug therapy. Tyrosine kinase inhibitors (TKIs) are known to suppress tumor angiogenesis by inhibiting vascular endothelial growth factor (VEGF). Furthermore, cabozantinib possesses inhibitory effects against AXL and mesenchymal-epithelial transition (MET) not seen with other TKIs. Consequently, cabozantinib may exhibit stronger anti-angiogenic activity than other vascular endothelial growth factor receptors (VEGFR) inhibitors. We report our experience with two cases of pneumothorax presumed to be related to cabozantinib in patients with renal cell carcinoma presenting with lung metastases.</p> Case presentation <p>A 59-year-old-asian-woman with renal cell carcinoma developed pneumothorax 4&#xa0;months after starting cabozantinib. After drainage and subsequent bronchial embolization, cabozantinib was resumed, but the patient developed a contralateral pneumothorax. There was inadequate improvement despite multiple adhesive therapies; therefore, repeat bronchial embolization was performed.</p> <p>A 42-year-old-Asian-man with renal cell carcinoma developed a refractory pneumothorax 10&#xa0;months after starting cabozantinib, which required drainage for 3&#xa0;weeks.</p> Conclusion <p>Although drug treatment of kidney cancer with cabozantinib has made great progress in recent years, more careful symptomatic monitoring is needed for adverse events associated with this drug. Our results suggest the need to pay attention to the occurrence of pneumothorax, although it is rare.</p>