Background Storz Professional Image Enhancement System (SPIES) endoscopy is an optical method to enhance the visualization of microvasculature on the mucosal surface and characterize epithelial changes. Objective In this study, we aimed to detect sinonasal inverted papilloma (SIP) in the microvasculature and/or mucosa using SPIES endoscopy. Materials and methods A total of 115 subjects, including 80 patients with SIPs or nasal polyps (NPs) and 35 healthy controls were investigated using white light endoscopy (WLE) and SPIES endoscopy. All lesions were diagnosed by histopathological examination. We used Kappa index (kappa) to evaluate the agreement of WLE and SPIES endoscopy with the histopathology. The sensitivity, specificity, positive predictive value, and negative predictive value were independently determined. Results NPs were histologically confirmed in 44 subjects (55%, 44/80), identified by WLE in 41 subjects (51.3%, 41/80), and identified by SPIES endoscopy in 43 subjects (53.8%, 43/80). SIPs were histologically confirmed in 36 cases (45%, 36/80), defined by WLE in 24 cases (30%, 24/80), and identified by SPIES endoscopy in 33 cases (41.3%, 33/80). Among 36 SIP patients, 33 cases (91.67%, 33/36) had a small lobular sign. The diagnosis of SIP by SPIES endoscopy was in excellent agreement with histopathological diagnosis (kappa = 0.873), while the diagnosis of SIP by WLE was in moderate agreement (kappa = 0.563). Conclusions and significance SPIES endoscopy is a rapid and noninvasive live-imaging technique with a unique contrast to examine sinonasal mucosa, submucosa and microvasculature. Our study suggested SPIES endoscopy could detect SIP, and the small lobular sign could be a sensitive predictor of SIP diagnosis.