Renal cell carcinoma (RCC) is one of the most frequent malignancies of the adults. Its incidence has been increasing steadily by 2-4% each year. Up to 30% of patients present with metastases at diagnosis. It is a highly vascularized cancer because of the hypoxia-induced factor stabilization as a consequence of von Hippel-Lindau inactivation. Hypoxia-induced factor accumulation leads to transactivation of molecules involved in angiogenesis including vascular endothelial growth factor (VEGF) and platelet-derived growth factor. Sunitinib is an oral tyrosine kinase inhibitor that interacts with several angiogenesis receptors including platelet-derived growth factor receptors and VEGF receptors, and is approved for the first-line treatment in metastatic RCC. In terms of tolerability, patients treated with sunitinib showed a higher incidence of diarrhea, vomiting, hypertension, hand-foot syndrome, and neutropenia, a safety profile consistent with what had been observed in earlier phase studies. Axitnib is a potent and selective tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3, and is approved in the second-line setting for patients with metastatic RCC. The tolerability profile of axitinib is favorable. The most commonly reported treatment-related adverse events are diarrhea, hypertension, fatigue, nausea, and dysphonia. Bowel toxicity, especially pneumatosis intestinalis and bowel perforation, is very uncommon. In particular, the incidence of intestinal perforation or fistulae is not well known for sunitinib or axitinib. Here, for the first time, we report the incidence of rectovaginal fistula in a 57-year-old White woman, with RCC, following treatment with sunitinib and axitinib.