The two-hit model is a well-known mechanism for the inactivation of tumor suppressor genes in cancer and it has been assumed that chromosomal deletions are the second inactivating event. Large deletions are frequently found in cancer and can lead to the haploinsufficiency of the loci mapped to the deleted region. The study by Xue et al. demonstrated that hemizygous 8p deletions can attenuate the activity of multiple genes that control growth and promote tumorigenesis, and showed that the effect of large 8p deletions on tumor phenotype goes beyond the effects of the individual genes as the characteristics of a tumor are also influenced by the additive and/or combined effect of the haploinsufficiency of multiple genes. These convincing findings, demonstrating that the hemizygosity of a cluster of genes negatively regulates proliferation and promotes tumor growth, have opened up new study perspectives aimed at characterizing the genomic organization of this new class of tumor suppressor genes and their role in tumorigenesis.