Identification of oncogenic BRAF mutations in primary and metastatic melanomas supports a linear model of clonal evolution in cancer. Some mutational studies, however, have failed to identify BRAF mutations in metastatic tumors from patients with BRAFmutant primary melanomas. Using a combination of methods, Riveiro-Falkenbach et al. (2015) assert that technical issues, and not clonal heterogeneity, may explain prior discordant mutational results.