Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphological and immunophenotypic features of mature tissue histiocytes. As HS may mimic non-Hodgkin lymphoma (NHL) pathologically, before the era of immunohistochemistry, many previously reported cases were misdiagnosed NHL. Up to date, there are only a few reports delineating the cytological features in fine-needle aspiration or bronchoalveolar lavage, but not in the effusion fluid yet. Herein, we report the case of a 61-year-old male with a mediastinal tumor presenting with malignant pleural effusion. The effusion cytology showed atypical epithelioid (histiocytoid) cells, both in loose clusters and a dispersed pattern, with scanty admixed inflammatory infiltrate. Distinct from the benign histiocytes, these tumor cells exhibited evident cytological atypia, including irregular nuclear contours, significant nuclear pleomorphism, brisk mitotic figures, and apoptotic bodies in the Papanicolaou stain. With the Liu stain, most tumor cells showed abundant blue-gray cytoplasm, some with small cytoplasmic vacuoles and formation of pseudopods. Subsequent biopsies of the tumor nodules in the right lower lung and pleura showed diffuse sheets of neoplastic cells expressing CD4, CD45, CD68, and lysozyme by immunohistochemistry, confirming the diagnosis. Usually subtyping the lymphoma in the effusion fluid is not an important issue since most patients already have previously confirmed lymphoma. In rare situation, like our patient, the disease may present initially as a malignant effusion. Immunophenotyping using cell blocks and/or excisional specimens is mandatory for a definitive diagnosis.