Nonsense-mediated decay (NMD) is a cellular process that targets mRNAs carrying a premature termination codon (PTC) for degradation. The kinetics and cellular location (nucleus versus cytoplasm) of NMD had remained under debate. To answer this question, the authors used fluorescence in situ hybridization (FISH) to locate individual β-globin mRNAs within individual cellular compartments, thus obtaining temporal and spatial information on mRNA abundance in intact cells. They identified two mRNA populations within single cells. Most PTC-carrying β-globin mRNAs were degraded soon after nuclear export (<1 minute) close to the nuclear envelope. The remaining second population had a half-life of >12 hours, which is similar to that of PTC-free mRNAs, indicating that it had evaded NMD and was degraded in the cytoplasm by other mechanisms. The authors conclude that there is a spatially and temporally defined checkpoint for NMD that some mRNAs can bypass to escape further NMD surveillance.