Tumor suppressor genes were first identified in inherited cancer syndromes, and were later shown to be involved in sporadic cancer as well. Over a dozen tumor suppressor genes have now been discovered including a breast and ovarian cancer susceptibility gene, BRCA1. Germ-line mutation of tumor suppressor genes is associated with an inherited predisposition to a limited tumor spectrum, but somatic mutations in tumors are heterogeneous. The 16 characterized tumor suppressor genes are involved in diverse functions including cell cycle regulation, check point control, transcriptional repression, signal transduction modulation, and DNA repair. These studies demonstrate that disturbance in cell proliferation, genetic stability and cell death could all precede tumorigenesis.