BACKGROUND: Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) that is a part of the normal human skin flora. Even though it belongs to CoNS family, it can cause severe and destructive infections in a similar fashion to Staphylococcus aureus. Skin and soft tissue infections (SSTI), bacteremia and endocarditis are amongst the most common clinical presentations. Diagnosis and clinical presentation of infections caused by S. lugdunensis in cancer patients is limited. MATERIALS AND METHODS: We performed a retrospective chart review of 24 patients who had cultures positive for S. lugdunensis. Out of 24 patients, 14 patients were diagnosed with a true infection and 10 other patients were considered to be colonized with this pathogen. We analyzed clinical manifestation, treatment and response to therapy. RESULTS: SSTI was the most common presentation in our study patients. All patients diagnosed with SSTI had a prior surgery or an invasive procedure at the affected site. Five urinary tract infections (UTIs), one catheter-associated bloodstream infection, and a deep pelvic abscess were other reported infections in our study. We observed that S. lugdunensis remains susceptible to a variety of antibiotics, with all isolates susceptible to vancomycin and linezolid and most remain susceptible to fluoroquinolone and trimethoprim/ sulfamethoxazole. All 14 patients received antibiotics and improved. CONCLUSION In our case series, SSTI was common and diagnosed in 50% of the patients with clinically significant isolates for S. lugdunensis. This is consistent with prior studies indicating that S. lugdunensis is a significant pathogen in SSTIs. UTI was the second most common infection type in our patient population.