Diagnosis of primary spindle cell tumors of the spleen is challenging because of the limited immunologic and cytogenetic characterization of this rare entity. We report a case of primary follicular dendritic cell (FDC) sarcoma of the spleen in a 44-year-old woman. Indications for FDC included positive staining for CD21, Ki-M4P, CD14, and fascin. Expression of both standard FDC markers CD23 and CD35 was detected immunohistochemically using tyramide signal amplification. Cytogenetic analysis revealed multiple clonal chromosomal aberrations involving unbalanced translocations of chromosomes X, 3, 5, 7, 8, 9, and 10, leading to net gains at 3q, 7p, 8q, and 9q and net losses at Xp, 8p, 9p, and 10p. Loss at Xp has been described previously in another tumor with FDC features, suggesting that this aberration might play a common role in this malignancy.