Collectively, we highlight underrated functions of ARF, positioned at the crossroads of tumor suppression (Weber et al., 2000; Tago et al., 2005; Kawagishi et al., 2010) and development (McKeller et al., 2002; Churchman et al., 2011; Figure 2), that could be exploited at the therapeutic level, especially in tumors with non-functional p53. The gene discussed is CDKN2A; the disease is neoplasm.