Mantle cell lymphoma (MCL) is characterized by typical morphologic features and the CD5+, CD23-immunophenotype. However, some morphologically typical MCLs are CD23+. A t(11;14)(q13;q32) translocation is frequently found in MCL, leading to overexpression of cyclin D1. We studied the expression of cyclin D1 in 50 small cell non-Hodgkin lymphomas by real-time reverse transcription-polymerase chain reaction. Most cases with typical MCL morphologic features and immunophenotype gave a strong signalfor cyclin D1, whereas most typical chronic lymphocytic leukemias/small lymphocytic lymphomas (CLLs/SLLs) gave weak or no signals. Based on these results, we determined a threshold value for the diagnosis of cyclin D1-overexpressing MCL. Cyclin D1 expression in 17 lymphomas with conflicting data from morphologic examination and immunophenotyping was variable. The concordance of cyclin D1 measurements with morphologic features and immunophenotype in typical cases proves the usefulness of the method. Unexpectedly high values were found in few CLL/SLL cases and in many CD23+ lymphomas with MCL morphologic features.