['This study developed a clinical decision rule (CDR) to rule in or rule out cystic fibrosis (CF) in the first weeks of life.', 'We combined a two-step nonconcurrent birth cohort and a cross-sectional controlled study in which observers and mothers were blinded to confirmatory sweat test results. Neonates from uncomplicated pregnancies and deliveries, with two subsequent tests for immunoreactive trypsinogen (IRT) higher than 70\xa0ng/mL, were eligible to take part.', 'We included 49 CF-affected and 177 CF-unaffected infants with an average age of 34\xa0days. CF-affected infants demonstrated statistically significant differences in weight gain, stool frequency and salty tasting skin from birth. Multivariate analysis showed that the main predictors of CF were salty tasting skin (odds ratio 17.2) and weight gain of <10.5\xa0g per day (odds ratio 4.6). Depending on the CDR score, we obtained the following results: sensitivity (42.9-61.2%), specificity (89.6-96.5%), positive (62.5-77.8%) and negative (85.6-89.1%) predictive value and positive (5.8-12.3) and negative (0.4-0.6) likelihood ratio.'] Is from lip to lab : salty tasting skin the main clue that raises clinical suspicion of cystic fibrosis in young infants?