In the 19th century, Rudolph Virchow observed that tumours often arise at sites of chronic inflammation. By now it is well known that inflammation can indeed drive tumourigenesis. One of the molecules implicated in this process is the cytokine tumour necrosis factor-alpha (TNF-α), which is associated with the inflammatory immune response and exerts pro-tumourigenic signals through the activation of TNF receptor 1 (TNFR1). The nuclear factor kappa B (NF-κB) signalling pathway is activated by TNF-α and is a key mediator of the immune response. But is this pathway also involved in inflammation-induced tumourigenesis? Data presented on page 3665 by Caroline Lee and colleagues suggest that it is. TNF-α induces gene expression of FAT10 (officially known as UBD) through activation of the NF-κB pathway in two colorectal cell lines. FAT10 then leads to an abbreviated mitotic phase and inhibits the association of the spindle checkpoint protein Mad2 with the kinetochore. In addition, increased FAT10 gene expression results in genomic instability and an increase in the number of cells with abnormal chromosome numbers. Finally, the researchers report that FAT10 is involved in protecting cells against TNF-α-induced cell death. Taken together, these observations provide a mechanism for tumour formation following chronic inflammation and highlight a potential therapeutic target for the treatment of such cancers.