MiRNAs are powerful biomarkers for detecting various diseases from tissue and body fluids. The potential of these molecules to monitor patients over time has, however, been less explored. We followed the fate of the plasma miRNome of lung cancer patients starting prior to surgery and ending 18 mo after surgery, with blood taken at three-month intervals. Principal component and clustering analysis showed that the differences of the overall miRNA patterns between the different time points were significantly smaller than between patients. For each patient we found a rather specific fluctuating miRNA pattern. We identified miRNAs that showed a significant correlation between expression level and time distance from surgery. A network analysis revealed 12 correlated miRNAs regulating 48 genes that were deregulated in lung cancer tissue. Our data underline the importance of studies that follow the fate of miRNAs over time, both to further our understanding of the biology of miRNA signatures and to establish these signatures as biomarkers.