Abstract In this chapter, we analyze the problem of genetic polymorphism in tumorigenesis, which determines basic capacities of tumors. The study of genome polymorphism with modified PCR methods allows the detection of various forms of polymorphism in tumor cells. This method has made it possible to determine association of DNA polymorphism with conditions of oncogenes, antioncogenes, and genes of apoptosis and with their allelic states. A special type of nonspecific DNA polymorphism that resulted from an increase in the mutation number in the cancer cell genome was discovered. This phenomenon was called the microsatellite mutator phenotype. Because the type of DNA polymorphism correlates with various biological capacities of malignant tumors and has an important prognostic significance, the analysis of DNA polymorphism in benign and malignant tumors of different histogenesis will play an important role both in theoretical studies of cancer and in oncological practice. A modified B1-PCR was used to study the genome polymorphism in the mouse tumor cells. The gain of the band 470 bp and the loss of the band 600 bp were revealed in the hepatoma cell line MH-22a as compared with liver cells of C3HA mice. The differentiation of teratocarcinoma EC F9 cells to endoderm-like cells was not accompanied by any changes in the B1-AF DNA fingerprint.