Sensitive methods as well as mathematical models, like the Luria-Delbrück model, led to the identification of pre-existing resistant subclones prior to therapy in some tumour entities: In non-small cell lung cancer the EGFR resistance mutation p.T790M and in colorectal carcinoma secondary KRAS mutations down to a frequency of 0.01% [7,8]. Here, KRAS is linked to colorectal carcinoma.