- Granular cell tumors (GCTs) are benign Schwann cell-derived neoplasms occurring throughout the body. Vulvar GCTs are usually isolated, but occasionally multifocal. On account of their anatomic location, surgical interventions aiming for negative resection margins can result in significant morbidity. We describe the clinicopathologic features of 17 vulvar GCTs in 13 patients followed for an average of 7 years. The average age at presentation was 46 years, and 84% of the patients were black. The tumors were multifocal in 3 (23%) patients, and all, either at presentation or subsequently also developed extravulvar foci. Patients with multifocal vulvar GCTs were nearly 10 years younger at presentation than patients in whom the disease was isolated. The most common complaint was a slow-enlarging mass occasionally associated with pruritus or overlying hyperpigmentation. Clinically, the tumors were subcutaneous, mobile, and nodular (2.1 cm on average), without overlying ulceration, and most often were found in the labia majora (6/17). The neoplasms were histologically heterogeneous, but exhibited either a predominantly nodular (3/17) or infiltrative (13/17) pattern of invasion. Cytologically, the tumors displayed round to polygonal cells with a granular cytoplasm, small hyperchromatic nuclei with minimal pleomorphism, and less than 2 mitoses per 10 high power fields. One tumor (1/17) consisted of cells with predominantly vesicular nuclei and prominent nucleoli and was classified as an atypical vulvar GCT. All tumors so examined were reactive for S-100 protein. Eight of 17 tumor excision specimens had positive margins. Of these, 5 tumors remained stable whereas the other 2 with follow-up progressed to require reexcisions after periods of 14 and 8.0 years, respectively. All patients with excisions with negative margins remained stable. Patients with multifocal tumors did not have a higher risk of recurrence per tumor, compared with patients with isolated disease, regardless of the margin status. No patient died from her disease. As granular cell neoplasms have such a low risk or recurrence and behave generally in an indolent manner, aggressive therapy is usually unwarranted.