Park I, et al. - A 29-year-old patient with a locally advanced Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) was reported in this work. Following initial administration of temsirolimus, surgical removal of kidney, retroperitoneal lymph nodes, inferior vena cava, and tumor thrombi was done. Unfortunately, he showed multiple liver metastases following 1 month after surgery, so was administered axitinib, which failed immediately. Bevacizumab plus erlotinib was then tried, which led to long-term good response that lasted more than 18 months. He is alive with disease and is continued on bevacizumab plus erlotinib treatment for maintenance. Results, in this case, suggest the possible validity of combined bevacizumab plus erlotinib for treating advanced HLRCC-associated kidney cancer, even after failures of mammalian target of rapamycin inhibitor and/or vascular endothelial growth factor receptor tyrosine kinase inhibitors based therapies.