We present a case of diffuse large B-cell lymphoma characterized by areas exhibiting unexpectedly low Ki67 staining in a 47-year-old man. No histologic or cytologic differences are observed between the areas with low and high proliferation index. With an alternative Ki67 clone, the proliferation index was significantly higher, revealing an additional Ki67 weakly positive population. Our findings suggest a potential partial false-negative staining of tumor cells for Ki67. The phenomenon of false-negative immunohistochemical staining has been described in the literature, especially for MYC protein and Bcl2. In the studies, the phenomenon of false negativity was explained by MYC gene polymorphism leading to disruption of the commercial antibodies-binding epitope. To our knowledge, false-negative Ki67 staining has not been described in the medical literature. While Ki67 is regarded as a reliable proliferation marker, it is important to be aware of this rare potential pitfall to avoid a diagnostic misinterpretation of such tumors as indolent B-cell lymphomas, especially in small limited biopsies.