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The diagnosis of systemic lupus erythematosus (SLE) has undergone radical change after the development of serological techniques. The in vitro demonstration of lupus erythematosus (LE) cell has less significance for the diagnosis of SLE in the present scenario. Although over the years, the spontaneous in vivo occurrence of LE cell in numerous body fluids as an initial presentation of SLE has been documented. The report of the presence of the LE cell can not only aid in the further workup of the patient but also suggest the involvement of a particular organ or body cavities by SLE. The morphology and mimickers of the LE cell should be cogitated and meticulous search of such cells should play an important role in the evaluation of body fluids. In our case, the patient presented at emergency with pericardial tamponade and cytological evaluation of the pericardial fluid demonstrated in vivo presence of LE cells. The serological work‐up then confirmed the case to be SLE. This report and review of literature wish to highlight the fact that this cell still plays a significant role even in the era of immunoassays.