BRAF and malignant colon neoplasm: As the two mutations tend to be mutually exclusive (Rajagopalan et al, 2002; Yuen et al, 2002), KRAS is inferred to signal principally through BRAF in colon cancer cells, leading to an assumption that tumours with KRAS or BRAF mutations may be equally vulnerable to inhibition of BRAF. Our finding that the natural history and treatment response of BRAF-mutant tumours differ markedly from all others implies that BRAF mutation does not simply substitute for KRAS activation in a linear signalling pathway but probably confers additional or distinct properties, with ominous consequences.