In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here the authors used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Taking advantage of the comprehensive genomic annotation of each case, they used innovative statistical approaches to identify potential novel myeloma subgroups. They observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication. Therefore, next-generation sequencing allows analysis of the integrated spectrum of gene mutations, aneuploidies and IGH translocations in multiple myeloma. Also, karyotypic events have a stronger impact on prognosis than mutations, but extended genotyping shows novel prognostic categories.