Increasing evidence has shown that Darwin's theory of evolution provides vital insights into the emergence and etiology of different types of cancer. On a microscopic scale, cancer stem cells meet the conditions for the Darwinian process of natural selection. In particular, cancer stem cells undergo cell reproduction characterized by the emergence of heritable variability that promotes replication and cell survival. Methods: Evidence from previous studies was gathered to compare Burnet's clonal selection theory with the tumor evolution theory. Results: The findings show that the Darwinian theory offers a general framework for understanding fundamental aspects of cancer. As fundamental theoretical frameworks, Burnet's clonal selection theory and the tumor evolution theory can be used to explain cancer cell evolution and identify the beneficial adaptations that contribute to cell survival in tissue landscapes and tissue ecosystems. Conclusions: In conclusion, this study shows that both Burnet's clonal selection theory and the tumor evolution theory postulate that cancer cells in tissue ecosystems evolve through reiterative processes, such as clonal expansion, clonal selection, and genetic diversification. Therefore, both theories provide insights into the complexities and dynamics of cancer, including its development and progression. Finally, we take into account the occurrence of biologic variation in both tumor cells and lymphocytes. It is important to note that the presence of lymphocyte variations appears to be advantageous in the framework of tumor defense but also dangerous within the framework of autoimmune disease development.