Perineuriomas are uncommon benign peripheral nerve sheath tumors that include soft tissue, sclerosing, and intraneural variants. Fewer than 50 soft tissue perineuriomas have been reported to date, and the clinical significance of atypical histologic features is unknown. To characterize these tumors further, 81 soft tissue perineuriomas received between 1994 and 2003 were retrieved from the authors' consult files. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring physicians. Forty-three patients were female and 38 male (mean age, 46 years; range, 10-79 years). Tumor size ranged from 0.3 to 20 cm (mean, 4.1 cm) in greatest dimension. Most patients presented with a painless mass. The tumors arose in a wide anatomic distribution: 36 lower limb, 19 upper limb, 15 trunk, 7 head and neck, 3 retroperitoneum, and 1 paratesticular. Forty-two tumors were situated primarily in subcutis, 25 in deep soft tissue, and 9 were limited to the dermis. Nearly all cases were grossly well circumscribed; 12 showed focal microscopically infiltrative margins. Most tumors had a storiform and focally whorled growth pattern; 17 exhibited fascicular areas. Thirty-eight tumors were hypocellular, 15 were markedly hypercellular, and 7 showed alternating zones of hypocellularity and hypercellularity. Stroma was usually collagenous but in 17 tumors was predominantly myxoid, and in 16 was mixed collagenous and myxoid. Mitoses ranged from 0 to 13 per 30 high power fields (mean, 1); 53 tumors had no mitoses. Based on worrisome cytologic or architectural features, 14 cases were classified as atypical perineuriomas: 12 contained scattered pleomorphic cells, 1 showed an abrupt transition from typical morphology to a markedly hypercellular, fascicular area with cytologic atypia, and 1 exhibited diffuse infiltration of skeletal muscle. All tumors were reactive for epithelial membrane antigen; 50 of 78 (64%) expressed CD34, 22 of 76 (29%) claudin-1, 16 of 77 (21%) smooth muscle actin, and 4 of 81 (5%) S-100 protein. All tumors were negative for glial fibrillary acidic protein, neurofilament protein, and desmin. Clinical follow-up was available for 43 patients (mean, 41 months; range, 6-146 months). Among tumors for which the status of surgical margins was known, 52% were widely excised, 31% were marginally excised, and 18% had positive margins. Only two tumors recurred locally (one of which was atypical): one recurred 10 years following primary excision; and one recurred twice, 5 and 9 years following excision. No tumor metastasized. Soft tissue perineuriomas behave in a benign fashion and rarely recur. Atypical histologic features (including scattered pleomorphic cells and infiltrative margins) seem to have no clinical significance and appear to be akin to those seen in ancient schwannoma and atypical (bizarre) neurofibroma.