Genetic and environmental factors are responsible for the genomic lesions that cause cancer, a complex genetic disease associated with genomic instability. Studies aimed at deciphering the lesions in cancer have focused mainly on one or a few genes, despite the genomic scope of the disease. The recently decoded human DNA sequence is anticipated to foster understanding of human evolution and disease and the role of environment and heredity in the human condition. This review addresses the opportunities and challenges that the availability of the human genome sequence holds for cancer research.