Background: In the diagnostic work-up of lupus erythematosus (LE), direct immunofluoresence (DIF) examination could be helpful. Classically, clinically red lesions are targeted by clinicians in the hope of yielding an informative DIF result. However, the investigative correlation between the degree of inflammation and DIF positivity has never been published in the literature. Objective: In this study, we sought to discover if histologically inflamed lesions correlated with DIF positivity results. Method: We studied 112 lesions histologically consistent with LE and correlated the degree of histologic inflammation on the DIF hematoxylin and eosin-stained biopsy with DIF positivity. The degree and location of the inflammation, as well as the involvement of the dermoepidermal interface, were documented. Results: A positive lupus band test was defined as the presence of either (1) granular IgG alone ± other immunoglobulins and/or C3 or (2) granular IgM or Ig A plus other immunoglobulins ± C3. Fifty-four of 112 (48%) cases had positive DIF (DIF+) results, 26 of 112 (23%) had negative DIF (DIF-) results, and 32 of 112 (29%) had nonspecific DIF patterns. Of the DIF+ cases, 41 of 54 (76%) showed some degree of inflammation, whereas 25 of 26 (96%) DIF- cases had inflammation ( p − .60). Most of the biopsies in the study (85%) were inflamed, but the degree and location of the inflammation had no influence on DIF+ results. The intensity of the DIF+ band further failed to show any relationship with the degree of inflammation. Conclusion: The level of inflammatory activity in a clinical lesion fails to correlate with DIF positivity. Furthermore, other common histopathologic findings of LE are not predictive of DIF results.