Darwin's Theory of Evolution: inherited variation, natural selection and adaption to survive in the environment is vividly manifested by the process of cancer cell evolution. For each step from precancerous lesion to cancer in situ and metastasis, cancer cells continuously mutate and subclones are selected by the pressure from tumor microenvironment. Cancer is characterized by heterogeneity, which is also a reflection of cancer cell evolution. Renal cell carcinoma (RCC) is one of the most common tumors in urinary system and the incidence rate of RCC is rising in recent years. Because RCC is not sensitive to radiotherapy or chemotherapy, systemic targeted therapy is the only option for patients with advanced RCC. This paper reviews the significant molecular events during the evolution of RCC, revealing the high heterogeneity of RCC both in different patients and in the tumor itself. Understanding the characteristics of RCC evolution is a must to search specific molecular markers for early diagnosis and for practice of individualized therapy.