Traditionally, xenograft models have been used to study tumors in vivo. However, their utility is reduced by the use of tumor cell lines for implantation. Tumorgrafts (TGs; also known as patient-derived xenografts (PDXs)), which involve patient-derived tumor samples, are increasingly recognized as more representative models than traditional xenografts. Furthermore, we showed previously that renal cell carcinoma (RCC) TGs retain the histology, gene expression, DNA copy number alterations, mutations and treatment responsiveness of patient tumors. In skilled hands, implantations require ≤5 min per mouse, and TGs typically grow to 1 cm in 1–4 months. Here we outline the process of implantation of patient-derived RCC samples into the kidneys of immunodeficient mice, as well as the s.c. implantation for preclinical drug testing, including guidelines for the design and execution of drug trials. TGs have extensive applications besides therapeutic studies and may identify biomarkers and mechanisms of resistance. In addition, they may provide insights into tumor biology.