The majority of cases are caused by the Nocardia asteroides complex (at least 50% of invasive infections). The N. asteroides complex is comprised of N. abscessus, N. cyriacigeorgica, N. farcinica, and N. nova. Other known pathogenic species of Nocardia include N. transvalensis complex, N. brasiliensis, and N. pseudobrasiliensis.

Pulmonary, disseminated and CNS infections are acquired through inhalation; primary cutaneous disease is acquired through inoculation of the skin. Rarely, nosocomial postsurgical transmission occurs.

Normally found in soil, these organisms cause occasional sporadic disease in humans and animals throughout the world. The usual mode of transmission is inhalation of organisms suspended in dust. Transmission by direct inoculation through puncture wounds or abrasions is less common. Generally, nocardial infection requires some degree of immune suppression.