BACKGROUND To evaluate the incidence and impact of early post-chemoradiation (cRT) 'pseudoprogression' (PsPD) amongst glioblastoma multiforme (GBM) patients treated with the current standard of care - 60 Gy conformal radiotherapy with concurrent low-dose temozolomide, followed by six cycles of high-dose temozolomide (the 'Stupp protocol'). METHODS Clinical notes and radiology reports for GBM patients treated as per the Stupp protocol were reviewed. PsPD was defined as apparent radiological progression on the first post-cRT scan, with further imaging within 3 months being stable or improving, while true early progression (ePD) was confirmed by continued progression in the subsequent 3 months following the first post-cRT scan. RESULTS Of the 68 patients evaluated, 14 (21%) and 27 (40%) experienced PsPD and ePD, respectively; 3/14 (21%) patients experiencing PsPD and 14/27(52%), ePD were symptomatic for progression on first post-cRT follow-up (P = 0.096 for difference). Median survival for patients with ePD, PsPD and neither were 10.4, 27.4 and 13.0 months, respectively (P = 0.003 for ePD vs. PsPD, P = 0.19 for neither vs. PsPD groups). CONCLUSIONS These data confirm a significant incidence of PsPD in post-cRT GBM patients, associated with improved median survival compared with those with neither ePD nor PsPD (not statistically significant). It appears likely that PsPD actually represents tumour response, conflicting with the traditional notion that increase in lesion size on contrast-enhanced imaging represents disease progression. Early post-cRT imaging should thus be interpreted with caution. Accompanying clinical symptoms are more commonly associated with ePD, but do not reliably distinguish PsPD from ePD.