The aim of this study was to perform translation, cross-cultural adaptation, and validation of the sinonasal outcome test 22 (SNOT-22) in the Greek language. SNOT-22 was translated into Greek. A prospective study was conducted on adult patients with chronic rhinosinusitis (CRS) according to rhinosinusitis and nasal polyps (EPOS) criteria. Test-retest evaluation of the patients was carried out. Internal consistency was assessed with Cronbach's alpha test, and test-retest reliability with Pearson's test (parametric correlation coefficient), kappa (reproducibility) and Bland-Altman plot (extent of agreement). Validity was assessed by comparing scores between a control group of volunteers without CRS and the CRS group using Mann-Whitney test. Responsiveness was assessed on CRS patients who underwent surgery, by comparing preoperative to 3 months postoperative scores with paired t test. Furthermore the magnitude of surgery effect was evaluated. Test-retest evaluation was accepted in 64 patients. Cronbach's alpha was 0.84 and 0.89 at test and retest, respectively, suggesting good internal consistency. Pearson's correlation coefficient was 0.91 (p < 0.001), revealing good correlation between initial and retest scores. Mean kappa value was 0.65, indicating a high level of reproducibility, while in Bland-Altman plot the differences were located between agreement thresholds. The control group consisted of 120 volunteers. Mann-Whitney test showed a statistically significant lower score for the control group (p < 0.0001). 32 CRS patients underwent surgical treatment. Postoperative scores were significantly lower than preoperative (p < 0.0001) while the magnitude of surgery effect was considered high. Greek SNOT-22 is a valid instrument with good internal consistency, reliability, reproducibility, validity and responsiveness.