While the diagnosis of cystic fibrosis (CF) is often straightforward and reliant on correlation between genetic testing and clinical signs and symptoms, there is a subset where the distinction is not nearly as clearcut. This has previously been reported in patients identified through newborn screening but not meeting full CF diagnostic criteria, earning the label of CF Screen Positive, Inconclusive Diagnosis (CFSPID) instead. A homologous diagnostic category in adults is named CF Transmembrane Conductance Regulator-Related Disorder (CFTR-RD). Through a retrospective chart review, this study reports on a relatively large adult cohort (n=23) that presented to pulmonology clinic at a single center with intermediate or positive sweat chloride tests but non-diagnostic full CFTR gene analysis. Median sweat chloride result was 48 mmol/L, and a majority of the cohort had chronic lung disease with atypical pathogens on sputum culture, including Pseudomonas aeruginosa, non-tuberculous Mycobacteria, Acinetobacter species, amongst others. This clinical picture suggests CFTR dysfunction or similar mechanism in the absence of an identified genetic cause. Alternate chloride channels and their respective genes or candidates of genetic modifiers to the CF-phenotype could be targets of further research in this cohort or similar patients. Such genetic modifiers include loci that have been implicated in inflammation, the CFTR interactome, and/or co-/post-translational modification of CFTR.