We report a distinctive angiomyxofibromatous lesion arising from the falx cerebri of a 48-year-old woman. The tumor was composed of bland-appearing, spindle, and stellate cells in a myxoid matrix with prominent vascularity. The tumor cells were immunopositive diffusely for vimentin and focally for S-100 protein, but were immunonegative for epithelial membrane antigen, CD34, MIC2, Bcl-2, glial fibrillary acidic protein, cytokeratin CAM 5.2, desmin, and smooth muscle actin. This lesion could not be categorized according to the current World Health Organization classification of tumors of the nervous system, thus underscoring a need to enhance our understanding of myxoid mesenchymal neoplasms and reassess their nosology.