Background/Objectives: Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) commonly found on human skin. Unlike other CoNS, S. lugdunensis has a notable potential to cause severe infections comparable to Staphylococcus aureus. This study aimed to characterize the clinical and microbiological profile of patients with S. lugdunensis skin infections at a single center. Methods: We conducted a retrospective analysis of patient records from the Dermatology Department of the University Hospital of Heraklion, Greece, covering the period from January 2014 to January 2024. Patients’ clinical presentations, demographics, infection sites, comorbidities, prior infections, antimicrobial treatments, and therapeutic responses were examined. Specimens were collected, transported, and processed according to standardized microbiological protocols. Bacterial identification and antibiotic susceptibility testing were performed using the Vitek 2 automated system and MALDI-TOF MS, with results interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Results: A total of 123 skin specimens positive for S. lugdunensis were analyzed. The cohort comprised 62 males (50.4%) and 61 females (49.6%), with a mean age of 40.24 ± 20.14 years. Most specimens were collected from pus (84%), primarily from below the waist (66.7%). Hidradenitis suppurativa (26%) was the most common condition associated with S. lugdunensis, followed by folliculitis, abscesses, ulcers, cellulitis, and acne. Co-infections with other bacteria were noted in 49.6% of cases, and 25.2% of infections were nosocomially acquired. The majority of patients (65%) received systemic antibiotics, predominantly amoxicillin/clavulanic acid, cefuroxime axetil, and doxycycline, with a cure rate of 100%. All isolates were susceptible to several antibiotics, though resistance to penicillin (28.5%) and clindamycin (36%) was observed. Conclusions: S. lugdunensis is a significant pathogen in skin infections, capable of causing severe disease. The high cure rate demonstrates the effectiveness of appropriate antibiotic therapy. Continued monitoring and antimicrobial stewardship are essential to manage resistance and ensure effective treatment.