A fundamental question in cancer biology is how tumours initiate. Why does it take up to 10 years from the initial oncogenic event to the actual formation of tumours? Why are tumour rates still rising? And how come we all carry oncogenic mutation in our self – yet, luckily, we do not all develop tumours. The prevailing hypothesis of tumour initiation is that cellular transformation is achieved through sequential accumulation of oncogenic mutations a given cell. Here I will present evidence that an obese environment can act in combination with premalignant mutated cells to drive oncogenesis. And further, that a prior state of obesity can sensitize cells to future oncogenic events.