There is sparse literature demonstrating effective treatments for metastatic chromophobe renal cell carcinoma (ChRCC). The tyrosine kinase inhibitor (TKI) sunitinib selectively inhibits the VEGF pathway and it is a standard care for metastatic clear cell renal cell carcinoma (ccRCC), although data supporting its use in ChRCC is much more limited. A 56-year-old underwent palliative nephrectomy for locally-advanced ChRCC with sarcomatoid differentiation. Tumor gene expression profiling using Affymetrix HG-U133 Plus 2.0 GeneChip platform demonstrated significantly elevated VEGF-C expression compared to normal renal tissue (n = 12) and other types RCC (n = 158). Adjuvant sunitinib was used to treat his residual unresectable retroperitoneal lymph nodes. He demonstrated an exceptional response and underwent complete surgical resection four months later. He has been managed with TKIs for nearly nine years with only minimal disease progression. Additional studies exploring treatment options for patients with non-clear cell RCC are needed; in their absence, we would recommend TKIs for patients whose tumors bear a similar molecular profile.