Infectious pseudotumors are unusual proliferations of histiocytes in response to certain microbial organisms. Occasionally this process may involve large airways, producing a mass lesion that may cause respiratory obstruction. Infectious pseudotumors can be confused with malignancy in their radiologic appearance and clinical presentation. We present a case of an aggressive endotracheal pseudotumor associated with Rhodococcus equi infection in a patient with advanced HIV disease. Microscopically, the lesion was composed of sheets of epithelioid histiocytes with large, strongly eosinophilic intra-cytoplasmic granules and features of malakoplakia. In this report, we review the literature of these unusual lesions and compare them to cases of conventional malakoplakia involving the large airways. We also explore the pathogenetic mechanisms that may contribute to the distinctive histologic appearance of Rhodococcus-associated pseudotumors.