The observation that 5-ALA fluorescence is dependent on the activity of HO-1, which in turn is dependent of the activity of EGFR, is clinically relevant as it underlies the clinical findings of possible low or absence of fluorescence to the naked eye as reported by Hauser et al. Thus, together our findings suggest that intra-tumoral heterogeneity of EGFR/EGFRvIII expression might explain the intra-tumoral variability in 5-ALA induced fluorescence expression, resulting, as previously reported, in false negative areas of tumor infiltration [10, 23]. The gene discussed is EGFR; the disease is neoplasm.