Cancer arises as a result of accumulation of genetic changes in a single cell. This is the basis of gene mutation theory of cancer. A small number of gene mutations drive cancer, and cancer cells are addicted to these oncogenes. Cancer cell dies when there is no continued oncogene expression. This oncogene addiction concept is the basis for the development of molecularly targeted agents. We have a number of success history such as imatinib in chronic myelogenous leukemia CML or crizotinib in ALK-positive lung cancer. However, these are not common at all. Why not? We expected that cancer genome sequencing (CGS) project will reveal all gene mutations in tumors resulting in the development of precise medicine in each patient. In reality, CGS has produced massive genetic data, however, we failed to identify commonly shared gene mutations. Why not? This book introduces a new concept of genome theory of cancer evolution, in an attempt to solve these challenges and paradoxes. By critically analyzing the currently available data, the author compared gene- and genome-based theories. This book will serve as an excellent resource for cancer researchers.