Immunohistochemistry is the most widely used approach in the diagnosis of mantle cell lymphoma (MCL). However, its reliability may be hampered by several technical reasons, necessitating the use of alternative techniques such as the identification of the t(11;14)(q13;q32) translocation to characterize such lesions. The authors compared two monoclonal antibodies (DCS-6 and SP4) for assessing cyclin D1 immunoreactivity in a series of 22 MCLs. Their results documented that SP4, a novel rabbit monoclonal antibody, is more effective than the mouse monoclonal antibody DCS-6, one of the most commonly used reagents in daily practice. Although DCS-6 and SP4 were capable of identifying cyclin D1 immunoreactivity in 95.4% and 100% of the cases analyzed, respectively, the prevalence of cyclin D1 immunoreactive neoplastic cells was significantly (P < 0.0001) higher with SP4 (86.6 +/- 13.1%) than with DCS-6 (39.8 +/- 32%). Moreover, the staining intensity was faint in 16 (76.2%) cases and moderate to strong in 5 (23.8%) cases immunostained with DCS- 6, while all the cases showed a moderate to strong immunoreactivity with SP4 (P < 0.0001). According to an arbitrary score based on the percentage of immunoreactive neoplastic cells and staining intensity, only 10 (45.4%) cases were considered high cyclin D1 expressors after staining with DCS-6, whereas all the cases were high expressors with SP4 (P < 0.0001). These data provide evidence that the SP4 monoclonal antibody may be a fast, easy-to-interpret, and reliable surrogate for the detection of the (11;14) translocation by molecular techniques.