Mantle cell lymphoma (MCL) is a rare, specific lymphoma subtype. Though the morphologic and immunophenotypic features of MCL have been well described in recent literatures, it is still a diagnostic dilemma because of its frequent confusion with other small B cell lymphomas (SBCLs). In the present study, we primarily focus on establishing a sensitive and specific method for the diagnosis of MCL, which is efficient to distinguish this disease from other SBCLs. We carried out our investigation for MCL and other SBCLs (including SLL, FL, MZL, and MALT) on their feature of morphology, immunophenotype, and t(11;14)(q13;q32) translocation analysis based on polymerase chain reaction (PCR) and interphase nuclei micro-array fluorescence in situ hybridization (FISH). The morphologic and immunologic analysis showed the positive rate of cyclin D1 was 76.47% in MCL, which was significantly higher than that in other SBCLs. The positive rate of t(11;14) translocation was 25.81% and 35.48%, respectively, tested by general and semi-nested PCR, while 93.10% positive rate was shown with low background and strong signals pattern when tested by Nuclei micro-array FISH. Our research shows that t(11;14) translocation is a special and useful diagnostic marker for MCL, and detection of the marker by nuclei micro-array FISH is convenient and economic, especially more sensitive and specific than other methods for the diagnosis of MCL.