Successful diagnosis of mantle cell lymphoma (MCL) by immunohistochemistry is largely dependent on the successful demonstration of cyclin D1 overexpression in cases that fit clinical, morphologic, and immunophenotypical profiles. Accurate diagnosis in these cases is important due to the aggressive progression and poor survival times associated with this type of lymphoma. However, demonstration of cyclin D1 by immunohistochemistry on formalin-fixed, paraffin-embedded tissue is often fraught with technical difficulties, chiefly poor staining intensity largely due to insufficient antigen retrieval. The authors report a simple antigen retrieval technique that combines both heat and enzymatic treatment to demonstrate cyclin D1 overexpression. Furthermore, it appears that the antigen retrieval method is the key factor in the demonstration of cyclin D1, as detection systems with differing sensitivities (labeled streptavidin biotin [ABC] and dextran polymeric conjugate [Envision]) fail to demonstrate any significant differences in their staining intensities. This isa simple, cost-effective method that can be performed manually or can easily be adapted to suit automated staining systems.