The involvement of NF-Y in cancer is underpinned by its role in proliferation, the presence of inverted CCAAT-boxes in the promoters of many cancer-associated genes and interaction with and regulation of cancer-related proteins, including c-fos, wild type and mutant p53, p73, ΔNp63α, p21, Ash2L, BRCA-1, cMyc, Sox9, lamin, ZHX1/2 and in particular the ubiquitous cancer-related transcription factor Sp1 [6–11]. The gene discussed is MYC; the disease is cancer.