A Cancer Genome Atlas project study has analysed 3,527 specimens of 12 cancer types using five different genome-wide platforms and one proteomic platform. The analysis revealed that the tumours could be classified into 11 molecular subtypes, five of which were similar to their tissue-of-origin counterparts; however, other novel molecular subtypes encompassed cancers from diverse locations, such as squamous-like lung, head and neck, and bladder cancers. Classification of cancers into subtypes with distinct molecular profiles might provide multiple opportunities to improve disease management compared with tissue-of-origin classifications; for example, by informing prognosis and guiding patient enrolment in clinical trials of molecularly targeted therapies.