Sclerosing epithelioid fibrosarcoma (SEF) is a rare mesenchymal neoplasm defined in the WHO classification of soft tissue tumor as a "rare malignant fibroblastic neoplasm characterized by epithelioid fibroblasts arranged in cords and nests and embedded in a dense sclerotic hyalinized stroma." These morphological features are associated with a unique immunohistochemical pattern (particularly MUC4 hyperexpression) and with characteristic gene rearrangements, mostly involving EWSR1 and CREB3L1 or CREB3L2. If it usually arises in deep soft tissues of various locations, SEF has also been reported in bones or viscera. Nevertheless, to our knowledge, no primary brain location has been described. Here, we report a left occipital SEF arising in a middle-aged woman with no evidence of systemic location after a comprehensive clinic-radiological assessment. We discuss the main differential neuropathological diagnoses and provide a comprehensive genetic and epigenetic description of this tumor comparatively to the more frequent systemic locations.