Several genetic events are necessary for a cell to become malignant. Some of these events are activation of proto-oncogenes, and other events are loss of normal function of tumor suppressor gene(s). Two or more different tumor suppressor genes may be inactivated in some tumors, and the same suppressor gene may be involved in different types of tumors. Loss of constitutional heterozygosity (LOH) in the tumor suggests that a certain tumor suppressor gene may reside near the locus of the probe by which the LOH was demonstrated. However, LOH is not necessarily found when a tumor suppressor gene is inactivated. The frequency of LOH found by a probe depends upon the distance between the probe and the tumor suppressor gene. Moreover, inactivation of the suppressor gene by point mutation or very small deletion does not cause any change in electrophoretic mobility of the DNA fragment detected by the probe. Treatment of a cancer by tumor suppressor gene(s) is not possible until a technique by which we can introduce the gene into all the tumor cells is established. At present, clinicians should cooperate with basic scientists in the search for tumor suppressor genes. The comparison of clinical features and the genetic alterations in the tumor will shed light on the malignant behavior of the tumor cells such as rapid growth and/or tendency to metastasis.