Since the development of the polymerase chain reaction (PCR) method of DNA amplification in 1985, numerous improvements, modifications, and novel applications of PCR have been devised. These developments eventually made it possible to examine minute clinical samples. It has become clear that cancer arise and progress through the accumulation of various genetic alterations. Certain genetic changes are now considered to be molecular markers useful not only for early diagnosis but also for predicting the behavior of cancer and the clinical outcome of patients. Some molecular markers are also useful for diagnosis of inherited cancer and susceptibility to cancer. We describe the latest improvements of detecting these molecular markers and clinical application of them in digestive cancer.