Background/aim: Isolated sphenoid sinus-derived lesions are rare and generally present with unclear symptoms. We are sharing our experience to be mindful of such lesions in differential diagnosis and to help accomplish successful treatment while avoiding revisions and complications.Materials and methods: Data from patients who underwent isolated sphenoid sinus surgeries (ISSs) were retrospectively extracted from the period of January 2005 to August 2015. Demographic data, chief complaints and presenting symptoms, imaging findings, surgical management, and results were evaluated. Results: There were 40 patients who underwent ISS. These patients had different pathologies. The chief complaint was nonspecific headache, except for cerebrospinal fluid leak patients who presented with serous rhinorrhea. Conclusion: It is critical to investigate suspicious symptoms with clinical findings and imaging techniques to avoid late diagnoses of isolated sphenoid pathologies. The transnasal approach is more minimally invasive and tissue-sparing. In our experience, we have noted that excising the inferior one-third of the superior turbinate decreases revisions. On the other hand, results show that the presence of concomitant pathology and invasive fungal disease increases the risk of revision surgery and complications.