Recent evidence suggests that results from multiple-breath washout (MBW) using nitrogen (N2) as washout gas are different to those obtained by using sulfur hexafluoride (SF6). Explanations were mainly related to different MBW equipment and gas properties. We aim to mention a new aspect, namely using the same cut-off in both techniques to determine lung clearance index (usually 2.5% of initial tracer concentration) irrespective of additional contribution of tissue-nitrogen in N2-MBW. In a simple model calculation we subtracted 1% tissue-N2 from the N2-MBW in real washout traces from two children, one with cystic fibrosis (CF) and one healthy. This "SF6-washout simulation" decreased LCI differently in the children. In the healthy subject 1/40(th) (2.5%) was achieved two breaths earlier compared to the original signal and changed LCI from 6.7 to 5.9 (12%), while in CF 1/40(th) was achieved 19 breaths earlier leading to a LCI decrease from 13.7 to 10.0 (27%). It would have been required to wash out SF6 until 1/66(th) (1.5%) to be comparable to N2 washout at 1/40th (2.5%), or to stop N2-MBW already at 3.5% of the starting concentration to make both techniques comparable. We show that a basic physiological-mathematical difference between both techniques additionally accounts for different sensitivities and poor agreement between SF6- and N2-MBW. The best way of adjusting for the contribution of tissue-N2 needs to be examined in future studies. Thus, despite increasing use in different disease groups, the books on MBW technology are obviously not closed yet.