The ligand-stimulated endocytosis of EGF receptor (EGFR) is widely used in membrane trafficking studies as a marker of lysosomal targeting pathways. EGFR is overexpressed in multiple human cancers, and its endocytosis can be promoted by various stresses that induce DNA damage, including chemotherapeutic agents such as cisplatin. Thus, EGFR and its endocytosis are of great interest to cancer biologists. Here (p. 2481), Clare Futter and colleagues set out to investigate the fate of EGFR following different DNA-damage-inducing stimuli in HeLa cells and a head and neck cancer cell line in which EGFR is a relevant therapeutic target. The authors show that X-rays do not induce detectable translocation of EGFR to the nucleus in the two cell types. Although apparent nuclear staining with EGFR extracellular domain antibody is observed under certain conditions, it is shown to be artefactual. Importantly, cisplatin, UVB and UVA treatment induce EGFR endocytosis, but not X-ray or UVA treatment, despite all of these stresses inducing DNA damage. DNA damage alone, therefore, is not sufficient to induce EGFR endocytosis. Finally, the authors show that the ability to induce endocytosis does not correlate with the degree of DNA damage, but rather with the ability to activate p38 MAPK proteins. This study highlights the importance of rigorous controls in analysing receptor distribution.