- Objective: Staphylococcus lugdunensis is considered to be more aggressive than other coagulase-negative staphylococci (CoNS). There are gaps in knowledge regarding the importance of isolating S. lugdunensis from different sources and in different patient subsets. Our objective was to describe the spectrum, clinical manifestations, and outcomes of infections caused by S. lugdunensis in patients with cancer. Methods: A retrospective review of all cancer patients from whom S. lugdunensis was isolated in a pure culture from clinically significant sites. Results: Between 2011 and 2014, 2263 CoNS were isolated, of them 45 S. lugdunensis were isolated in a pure culture and were included in this analysis. Only three patients were neutropenic. Skin and skin structure infections (SSSIs) occurred most often (36 cases) followed by five blood stream infections, one of which had destructive endocarditis and four infections at other sites. Of the 36 SSSIs, 29 were related to surgical or invasive procedures, and six of these involved an implanted medical device. All isolates were susceptible to vancomycin, 98% to levofloxacin and 89% to oxacillin. All patients responded to the therapy. Conclusions: Cancer patients including those with neutropenia do not appear to have an increased frequency of infections caused by S. lugdunensis. SSSIs are predominant and are often associated with surgical procedures and/or implanted medical devices. Blood stream infections caused by S. lugdunensis are uncommon but may have an increased rate of serious complications such as endocarditis. Nevertheless, these organisms are generally susceptible to multiple classes of antimicrobial agents, and the overall response to therapy is high.