While the histologic features of alveolar soft part sarcoma and granular cell tumor are typically distinctive, occasional cases show significant morphologic overlap. Differentiating these entities is crucial, since granular cell tumor is almost always benign and alveolar soft part sarcoma is invariably malignant. We evaluated a panel of immunohistochemical stains (S-100 protein, inhibin, SOX10, nestin, calretinin, and TFE3) in 13 alveolar soft part sarcomas and 11 granular cell tumors. Tissue sections were also stained by the periodic acid-Schiff method after diastase digestion (PAS-D) and evaluated for coarse cytoplasmic granularity or crystalline cytoplasmic inclusions. S-100 protein, inhibin, SOX10, and nestin each distinguished granular cell tumor and alveolar soft part sarcoma with 100% sensitivity and specificity. PAS-D staining also distinguished cases with 100% accuracy, as granular cell tumor consistently demonstrated coarsely granular, PAS-D-positive cytoplasm and alveolar soft part sarcoma showed only focal intracytoplasmic crystalline inclusions. Although all granular cell tumors were calretinin-positive, so were 46% of alveolar soft part sarcomas. TFE3 was positive in 91% of granular cell tumors and all alveolar soft part sarcomas. Together with PAS-D, immunohistochemical stains for S-100 protein, inhibin, SOX10, and nestin accurately identify alveolar soft part sarcoma and granular cell tumor. Although TFE3 has been reported as a relatively specific marker for alveolar soft part sarcoma, it should be recalled that it is also expressed in most granular cell tumors as well.