The biologic and clinical heterogeneity of lymphomas represents the major obstacle to their diagnosis. Because histologic analysis, which is the initial diagnostic approach, has been demonstrated to be insufficient in the definition of certain types of lymphomas, molecular and immunologic techniques have been increasingly applied to obtain a precise diagnosis and to establish a correct treatment. Fluorescence in situ hybridization, in particular, is a powerful technique with many applications to the study of chromosomal rearrangements. In addition, because of their specificity and sensitivity, molecular techniques provide an important tool in assessing response to treatment, in detecting minimal residual disease, and in understanding the clinical and prognostic significance of the disease.