oncogenesis itself, which we define as the process by which normal cells acquire the characteristics of cancer cells. This definition encompasses the changes that occur prior to and after the threshold of cancer is reached. Normal cells evolve into cancerous cells partly as a result of selection acting on variation generated by genetic mutations that arise within multicellular organisms, which in turn result from exposure to mutagens, such as radiation and mutagenic chemicals, and errors in DNA replication. Over the past few decades, it has become apparent that a staggering number of mutations occur during oncogenesis and that the composition of these mutations usually varies greatly from cancer to cancer even among cancers of the same typeIt also stresses the importance of determining the scope of infectious causation of cancer, because individual pathogens can be responsible for multiple essential causes in infected cells.Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. Oncogenesis or cancer formation is the expression of impaired cellular events in the favor of uncontrolled cell growth and proliferation. This occurs basically by disruptions in harmonious control effects of the growth-inducing, growth-inhibiting, apoptosis-regulating, and DNA-repairing mechanisms. A simplified understanding of these mechanisms is given in this chapter. In the first part of the chapter, regarding the concepts of susceptibility to and formation of cancers, the basic knowledge of cellular genetic content and events is reviewed.In the second part, molecular basis of oncogenesis is explained regarding the eight hallmarks of cancers. For better understanding, well-described examples of mechanisms responsible in musculoskeletal system tumors are given through the text.