The Article by Xin Liu and colleagues1 published in The Lancet Oncology is the first randomised trial showing a benefit of site-specific therapy over empirical chemotherapy among patients with previously untreated cancer of unknown primary (CUP). Two previous randomised trials using a similar approach did not show any benefit of site-specific therapy over empirical chemotherapy.2 Liu and colleagues1 state that “site-specific prediction by the 90-gene expression assay might provide more disease information” and in their linked Comment, Greco and colleagues3 state that “gene-expression profiling guided therapy should emerge as a new standard of care in view of Liu and colleagues’ study”.