Myopericytoma is an uncommon, benign perivascular myoid cell tumor that occurs almost exclusively in somatic soft tissues. We report 2 cases occurring in patients with acquired immunodeficiency syndrome who show unusual clinical and biologic features. One patient presented with a bronchial mass and the other developed mass lesions of the tongue, vocal cord, and brain. Histologically, oval to plump spindly tumor cells with uniform nuclei and scanty cytoplasm formed sheets or cuffs around gaping or narrow vascular spaces. Focally, these areas merged into fascicles of more elongated cells with eosinophilic cytoplasm. The tumor cells were immunoreactive for actin but not desmin, and showed uniform labeling for Epstein-Barr virus (EBV) encoded RNAs on in-situ hybridization. Both patients were alive 5 years after incomplete excision of the lesions. In conjunction with another case reported in the literature, myopericytoma occurring in acquired immunodeficiency syndrome patients exhibits several features distinct from sporadic myopericytoma: presentation in anatomic sites other than somatic soft tissues, frequent presence of multifocal disease, and association with EBV. This tumor type therefore also broadens the spectrum of neoplasms associated with EBV.