B-cell neoplasias represent a heterogeneous group of diseases, including acute lymphocytic leukemia (ALL) and the broad spectrum of non-Hodgkin's lymphomas (NHL). Conventional cytogenetic analysis has revealed specific chromosomal aberrations in ALL as well as in NHL. Spectral karyotyping (SKY) is a novel molecular cytogenetic technique which allows the visualization of all human chromosomes in different colors, therefore greatly facilitating the recognition of chromosomal aberrations. The potential of SKY is exemplified by the fact that in our experience, 70% of the cases analyzed resulted in karyotypes where the majority of aberrations were either refined or new aberrations were detected when compared to their G-banding karyotypes. This also applies to the analysis of B-cell neoplasias. In hematologic malignancies, especially acute leukemias, specific chromosomal aberrations are of etiologic as well as diagnostic and prognostic importance. The identification of new recurrent chromosomal aberrations could therefore lead to a better characterization of disease entities or subgroups in ALL and NHL and further improve diagnosis, treatment stratification and ultimately prognosis. Interestingly, the comparison of the pattern of chromosomal aberrations in hematological neoplasias and carcinomas revealed striking differences. While about 50% of the aberrations in hematological malignancies are balanced translocations, such aberrations are exceedingly rare in epithelial cancers in which unbalanced structural and numerical aberrations prevail.