Background Melanotic schwannoma is a rare variant of schwannoma composed of melanin-producing cells with ultrastructural features of schwann cells. The description of the course of the tumors differs somewhat, but it is generally considered as a benign lesion. We investigated the clinicopathologic features, immunophenotypes, and ultrastructural features of 13 patients with nonpsammomatous melanotic schwannoma (NPMS).Methods Tumor specimens of each patient were sectioned and stained with hematoxylin-eosin, Fontana-Masson, Prussian blue, and periodic acid-Schiff (PAS). Immunohistochemical markers such as S-100, Leu-7, HMB-45, Melan-A, CK, EMA, vimentin, GFAP, laminin, collagen Ⅳ and MIB-1 were detected with the Envision immunohistochemical staining method. Four of the cases were observed by electron microscopy.Results Of the 13 patients, 8 were male and 5 female, aged from 11 to 92 years (mean, 38.6 years). The tumor sites included the spinal nerve root (5 patients), cranial nerve (1), greater omentum (1), subcutaneous tissue (3), mesentery (1), bone (1) and mediastinum (1). Eleven patients were followed up for over 2 years, with a mean of 5.9 years. One patient (9.1%) with a primary tumor in the greater omentum developed another primary tumor of the same type in the subcutaneous tissue of the abdominal wall after the first operation. Local recurrence of the tumor was seen in 2 patients (18.2%). One patient (9.1%) showed the local recurrence and metastasis. Seven patients (63.6%) showed no evidence of the recurrence or metastasis. Grossly, all tumors were well-circumscribed and the gross findings were suggestive of melanin-containing tumors. The tumor was composed of spindled and epithelioid cells with abundant intracytoplasmic melanin pigments. Nuclei were round and contained delicate, evenly distributed chromatins as well as small, distinct nucleoli. In some areas, the nucleoli were large and prominent. Rare mitoses were seen in most lesions except the larger omentum lesion. The pigment was shown to be positive for the Fontana-Masson and negative for Prussian blue and PAS. Immunohistochemical staining for S-100, Leu-7, HMB-45, Melan-A, and vimentin were strongly positive. Linear immunoreactions of both laminin and collagen Ⅳ was detected in all patients. Ultrastructurally, numerous elongated tumor-cell processes, duplicated basement membrane and melanosomes were observed in all developmental stages.Conclusions Histologically, melanotic schwannoma is a rare variant of schwannoma composed of melanin-producing cells with ultrastructural features of schwann cells. Distinguishing between this tumor and malignant melanoma is of paramount importance in planning of management. Immunohistochemically, combined use of laminin and collagen Ⅳ is valuable in distinguishing melanotic schwannoma from malignant melanoma. Wide local resection and additional radiotherapy should be advocated. Further studies including cytogenetic or molecular biology are still required to better delineate melanotic schwannoma from malignant melanoma. Appropriate long-term follow-up is needed for all melanotic schwannomas.