The purpose of this study was to develop a paranasal sinus CT scoring system that could be used as a diagnostic tool to discriminate cystic fibrosis (CF) patients from control patients examined for sinonasal disease. The model should include as few and easily applicable criteria as possible, supported by statistical analyses and clinical judgement. We used data from 116 CF and 136 control patients. The CF patients were grouped according to the number of confirmed CF mutations: genetically verified (CF-2), or based on sweat testing and clinical findings alone (CF-1, CF-0). Nine paranasal sinus CT criteria, including development, pneumatisation variants and inflammatory patterns, were evaluated. The final model included three criteria: (a) frontal and (b) sphenoid sinus development, and (c) absence of three pneumatisation variants. This model discriminated CF-2 from controls with overlap of summed scores in only 8 of 206 patients. When this model was applied in the CF-1 and CF-0 groups, two populations seemed to exist. A larger group with summed scores overlapping that of the CF-2 group and a smaller group with summed scores overlapping that of the control group. We conclude that this CT scoring system may support, as well as exclude, a CF diagnosis in cases of diagnostic uncertainty.