Pulmonary nocardiosis is an opportunistic infection that manifests itself mostly in the context of decreased defences, due either to pre-existing pathology or to immunosuppressive therapy, and is often complicated by central nervous system involvement. The clinical and radiological picture is highly variable, requiring a broad spectrum of differential diagnosis, and leaving a decisive and difficult role to the laboratory. We present two cases that exemplify the clinical variability of this infection, the difficulty of the microbiological diagnosis in a routine laboratory, the problems of the antimicrobials' selection, and the importance of a long therapy course.