Plexiform schwannoma (PS) is one of the least common histologic variants of schwannoma. It shows a plexiform growth pattern and typically occurs in the dermis and subcutaneous tissue. Morphologically, PS can display a conventional, cellular, or mixed appearance. However, the frequent cellular morphology associated with hyperchromatic nuclei, increased mitoses, and plexiform growth can suggest a malignant process, mainly a high-grade malignant peripheral nerve sheath tumor (MPNST). The purpose of this study was to analyze the clinicopathologic features of deep-seated PS and compare them with the superficial counterparts. Sixteen deep-seated PSs were analyzed clinicopathologically, immunohistochemically, and ultrastructurally, and compared with 8 superficial (5 dermal and 3 subcutaneous) PSs. There were 12 females and 4 males, ranging from 5 months to 61 years of age. Fifteen tumors were located in the deep somatic soft tissue (extremities, 8; retroperitoneum/pelvis, 3; trunk, 2; parotid, 1; vulva, 1) and 1 tumor was located in the thoracic esophagus. None of the patients had stigmata of neurofibromatosis. Local recurrence was noted in half of the patients with clinical information available, but none had evidence of disease at last follow-up. Worrisome morphologic features included: increased cellularity (68%), mild to moderate pleomorphism (50%), and mitotic activity (93%) ranging from 1 to 10 MF/10 high power fields (HPFs). Focal necrosis was seen in 12% and myxoid change was identified in 18% of cases. Immunohistochemical stains for S-100 protein showed strong and diffuse positivity on all cases tested. Ultrastructurally, findings characteristic of schwannian differentiation were identified in the cases analyzed. The 8 superficial PSs showed increased cellularity and mild to moderate pleomorphism in 62% of cases but lacked tumor necrosis. Deep-seated PS is a rare, under-recognized PNST of deep soft tissue, typically not associated with neurofibromatosis. Although commonly occurring in the extremities, they can be seen in other locations including the viscera. In contrast with the more common superficial (dermal and subcutaneous) tumors, deep PSs have a predilection for females, can occur in congenital settings, and can show necrosis and myxoid change. Common worrisome histologic features seen in both groups include increased cellularity and mitoses. It is important to differentiate these tumors from plexiform neurofibromas and MPNSTs as they follow a benign clinical course, with complete surgical excision being curative.