Introduction. Histiocytic sarcoma (HS) is a very rare and diagnostically difficult malignant neoplasm arising from dendritic cells and histiocytes. Its microscopic image is not specific, so the diagnosis of HS requires a wide panel of immunohistochemistry tests to exclude tumors with similar morphology, but of completely different origins. While diagnosing HS, cancers, other sarcomas, lymphomas and malignant melanoma should be excluded as well. Aim. The aim of this paper was to present a case of HS imitating tumor of the pancreatic tail in a 58-year-old woman. Case study. Intraoperative diagnosis was as follows: solid-cystic tumor of the pancreatic tail region, penetrating into the mesocolon and occluding the colon by pressing against it. Resection of the pathologic mass and tail of the pancreas, as well as total colectomy were performed. On the basis of postoperative histopathologic evaluation of the surgical specimen and a wide immunohistochemical panel, we excluded epithelial and myogenic origins of the tumor. Gastrointestinal stromal tumor, extramedullary myeloid tumor, lymphoma, neural tumors and malignant melanoma were also excluded. Histopathologic and immnohistochemical findings, compared to other authors’ findings led us to the diagnosis of histiocytic sarcoma. Complete resection of the tumor was performed, with sufficient margins of the healthy tissues. Physical examination and imaging performed three months after the surgery revealed features of the local recurrence, infiltration of the back wall of the stomach with a major compression of the gastric lumen. Metastatic foci in regions of left appendages and lower pole of the left kidney, multiple small hypodensic areas in the liver and enlarged paraaortal and mesenterial lymph nodes were also found. Discussion. HS is a very rare and diagnostically difficult malignant tumor. Microscopic image is non-specific, that is why the diagnosis of HS requires a wide histochemical panel to exclude tumors with similar morphology, but of completely different origins. Analysis of negative immunohistochemical studies, results of: CD68, LCA(CD45), CD4, CD30, CD31, Fascin, CD43, CD15, CD34, and comparing them with the results obtained by other authors led us to the diagnosis of HS. Clinical prognosis is negative and the most frequent course of the disease is aggressive. Conclusions. 1. Despite the rare prevalence of the tumor, there are numerous, well documented and immunohistochemically confirmed reports of histiocytic sarcoma and its gastrointestinal localization. That is why in a differential diagnosis of gastrointestinal tract-located tumors, sporadically occuring neoplasms should be also taken into account. 2. Diagnosis of HS requires a wide panel of immunohistochemistry tests to exclude tumors with similar morphology, but of completely different origins. 3. Recurrence of a neoplastic process in the described case confirms that, despite a surgical and microscopically total excision of the tumor, HS prognosis is negative and the course of the disease is very aggressive.