Isolated sphenoidal sinusitis (ISS) is a rare disease with non-specific symptoms and a potential for complications. Diagnosis is made clinically, endoscopically, and with imaging like CT scans or MRIs. This study aimed to evaluate if ISS meets the EPOS 2020 criteria for diagnosing acute rhinosinusitis and if new diagnostic criteria are needed. The study analyzed 193 charts and examination records from 2000 to 2022 in patients diagnosed with isolated sphenoidal sinusitis at the Ziv Medical Center in Safed, Israel. Of the 193, 57 patients were excluded, and the remaining 136 patients were included in the final analysis. Patients were evaluated using Ear, Nose and Throat (ENT), neurological and sinonasal video endoscopy, radiological findings, demographic data, symptoms and signs, and laboratory results. All these findings were reviewed according to the EPOS 2020 acute sinusitis diagnosis criteria and were analyzed to determine if ISS symptoms and signs fulfilled them. The patients included 40 men and 96 women, ranging in age from 17 to 86years (mean ± SD, 37 ± 15.2years). A positive endoscopy and radiography were encountered in 29.4%, and headache was present in 98%; the most common type was retro-orbital headache (31%). The results showed that there is no relationship between the symptoms of isolated sphenoidal sinusitis and the criteria for diagnosing acute sinusitis according to EPOS 2020. ISS is an uncommon entity encountered in clinical practice with non-specific symptoms and a potential for complications. Therefore, the condition must be kept in mind by clinicians, and prompt diagnosis and treatment must be initiated. This kind of sinusitis does not fulfill the standard guidelines for acute sinusitis diagnosis criteria.