The t(14;18)(q32;q21) translocation is the genetic hallmark of follicular lymphoma. Detection of this translocation can facilitate the diagnosis of follicular lymphoma and can be used to monitor response to therapy and level of residual disease. We herein review and compare practical techniques for detecting t(14;18)(q32;q21), including conventional cytogenetics, fluorescence in situ hybridization, Southern blot analysis, and polymerase chain reaction-based assay. Emphasis is placed on fluorescence in situ hybridization and polymerase chain reaction-based assay, given the applicability of these techniques to fixed, paraffin-embedded tissue.