Mechanisms of tumorigenesis and novel cancer therapies have been investigated in cultured mutant cells, genetically engineered to develop tumors, but the behaviour of these cells in a normal tissue environment remains almost completely unknown. In September 1 Journal of Clinical Investigation, Youyan Zhang and colleagues from Indiana University School of Medicine, Indianapolis, show that normal cells can strongly modulate the growth of mutant populations in vivo and this effect should be taken into account in experiments using only a homogeneous source of tumor-prone cells.