There is significant debate on the influence of inflammatory mucosal disease on paranasal sinus pneumatization (PSP) and temporal bone pneumatization (TBP) in cysticfibrosis patients (CF). It is often assumed that mucosal disease of the paranasal sinuses willnegatively influence development and pneumotization of the paranasal sinuses and temporal bone system. Methods: A case-control study of TBP and PSP in CF, chronic rhinosinusitis (CRS) and healthy control patients from a tertiary rhinology clinic. TBP and PSP were assessed by computed tomography (CT) using a previously validated scale. Genotype data for patients with CF was determined. Results: In total, 186 temporal bones and paranasal sinuses from 93 adult patients were assessed through evaluation of CT scans. Tha patients had a mean age of 43.4 ± 14.9 yrs. The interobserver correlation for TB scoring was 0.86. TBP did not differ between CF, CRS and controls (x2 = 6.93, p = 0.38). PSP was less in the CF group (x2 = 34.2, p < 0.001) than the CRS and control groups. CRS and controls did not differ in PSP. 51.6% of CF patients were homozygous for ?F508 and 16.1% were heterozygous. The ?F508 status correlated with poorer SP (x2 = 34.2, p < 0.001), but greater TBP (x2 = 14.9, p = 0.002). Conclusions: P.SP is impaired in CF and ?F508 homozygosity is related to poor PSP. TBP is well preserved in the CF population and ?F508 homozygosity correlates with greater TBP, with the underlying mechanisms being unclear. Genotype might play a role in skull base pneumatization.