It has been widely accepted that cancers were caused by gene mutations, which is the so-called somatic mutation theory (SMT).However, the SMT theory has received increasing doubts, disbelieves, and been facing challenges from other alternative theories.Therefore, from a pathological perspective, and with the evidences from molecular pathology,histopathology, and epidemiology, this study shows that the80-year-old paradigm of carcinogenesis process from atypia to in situ carcinoma to invasive cancer is incorrect.Since 90% of the human cancers are epithelially derived "carcinomas; the turnover of this paradigm naturally negates the SMT theory for SMT sits on this model.The invasive cancer grows out in the stroma de novo from misplaced stem cells, rather than deriving from the transformed in situ carcinoma cells.In addition, this study shows evidences that cancer cells are not "apoptosisresistant", but rather "short-lived sick cells".