Non-Hodgkin lymphomas (NHL), the 6th most frequent cancer in western countries, represent a large group of clonal proliferations derived from lymphoid cells. With available techniques, a large number of clinically and biologically distinct tumors are listed in the World Health Organization (WHO) classification. Disease definition is based on morphology, immunophenotype, genetic and molecular features, viral associations in certain cases, clinical characteristics and if possible the normal cell counterpart, which is an important determinant of lymphoma biology. Lymphomas derived from B-cells are by far most frequent, and NK/T-cell NHL account for < 10% of the cases. Recent technological and analytical advances in genetic, epigenetic and molecular profiling methods and next-generation sequencing technologies have markedly accelerated the characterization of lymphoma-associated molecular signatures and genetic profiles, and the discovery of genetic lesions, which collectively have greatly enhanced our understanding of lymphoma pathogenesis and are relevant to defining optimal therapies.