Background The purpose of this study was to identify the incidence of atypical Mycobacterium identified by routine sinus cultures and review the recent literature on management. Methods A retrospective case series was performed in a tertiary academic hospital. A retrospective case series of all patients treated with atypical Mycobacterium rhinosinusitis from 2005 to 2010 was performed. Cases were identified from a prospective database of 676 endoscopically guided sinus cultures. Results Eight patients with atypical Mycobacterium sinusitis were identified. There were five women and three men. Median age was 63 years (range, 55–71 years). All patients had prior endoscopic sinus surgery a median of 14 months (range, 0.8–162 months) before a positive culture result. Species identified included Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium abscessus, and Mycobacterium avium complex. Chief presenting symptoms were postnasal discharge (88%), followed by decreased smell and taste (63%), and facial pain/pressure (38%). Patients were treated based on sensitivity results with long-term oral antibiotics for at least 2 months based on improvements on endoscopy. Median follow-up for patients in this study after treatment was 1.3 years (range, 0.6–4.6 years). Conclusion In this study, atypical mycobacteria were identified in < 1% of sinus cultures. Prolonged, culture-directed antibiotic therapy remains the mainstay of treatment when there is clinical evidence of infection. Previous endoscopic sinus surgery may represent a risk factor for colonization and subsequent infection. Further research is necessary to determine the optimal treatment duration and management to prevent disease relapse