Abstract Objectives: To evaluate the need for routine histopathologic review of specimens obtained in uncomplicated endoscopic sinus surgery, and to suggest guidelines for obtaining histopathology. Methods: We reviewed the medical records of 790 patients who underwent 868 endoscopic sinus surgeries at this institution from 1986–2003. Indications for surgery were chronic sinusitis, recurrent acute sinusitis, nasal polyposis, or combinations of these diagnoses. All cases were considered routine, had failed medical therapy, and did not involve preoperative suspicion of neoplasm or other complicating factors (eg, encephalocele, prior sinonasal malignancy/mass lesion, infections with extranasal complications). All cases were reviewed for patient age, indications, laterality of disease, intranasal anatomy in unilateral cases, history of prior ESS, intraoperative suspicion of tumor, and final histopathology. Results: In 868 cases of endoscopic sinus surgery in which pathology was sent, neoplasm was found in 2 patients (lymphoma, inverted squamous papilloma). Final histopathology of all other specimens (99.77%) was consistent with inflammation and/or nasal polyposis. In 121 cases of unilateral disease, none were positive for neoplasm. Neoplasm was suspected intraoperatively in 12 cases, with all specimens demonstrating sinusitis and/or polyposis. In 277 cases involving bilateral nasal polyposis and 13 involving unilateral polyposis, no neoplasms were found. Conclusions: Based on our data and a review of the literature, histopathologic review of all specimens obtained in routine sinus surgery for polyposis and/or sinusitis is not indicated. Histopathologic exam should be conducted when: 1) there is intraoperative suspicion of tumor, 2) unilateral polyposis is present, 3) unilateral sinus opacification is present, 4) additional diagnostic information is needed (e.g. cultures, staging).