Nocardia infections are infrequently recognized in humans. Nocardia species may cause severe life-threatening infections among immunocompromised patients and have been reported to cause actinomycotic mycetomas, primarily in tropical areas. Two severely immunocompromised patients had disseminated N. transvalensis infections. One had underlying X-linked variant chronic granulomatous disease and died of disseminated N. transvalensis infection, which was diagnosed only at postmortem examination. The second patient developed N. transvalensis pneumonia within 3 months of undergoing renal transplantation and died of disseminated mixed Pseudallescheria boydii and N. transvalensis infections. Thus, N. transvalensis may cause invasive and potentially fatal pulmonary and disseminated infections. Accordingly, clinical microbiology laboratories should become proficient in identifying this uncommon aerobic actinomycete.