Mycobacterium avium complex (MAC) lung infection can mimic lung cancer nodules on routine chest imaging, leading to unnecessary invasive procedures. The authors describe three cases of patients with minimal or no symptoms where probable MAC infection was incidentally discovered requiring exclusion of malignancy. After an infectious cause was suspected, patients were empirically treated with azithromycin alone or in combination with other antibiotics. Treatment resulted in improvement in radiographic appearance of the nodules in size, density, or both, confirming an infectious etiology. This prevented more invasive examinations and surgical procedures. These cases illustrate the increasingly common infection, especially in the southeastern US. An empiric 3-month course of azithromycin in suspected MAC infection significantly shrinks nodules, confirming an infectious origin rather than malignancy.