This study aimed to assess the false-positive proportion of follow-up 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in lymphoma patients who initially achieved an end-of-treatment complete remission, using biopsy as reference standard. Medline was searched for original studies, studies were methodologically evaluated and results were meta analytically summarized. Proportion of false-positive results ranged between 9.5%-90.0%, with a weighted summary proportion (random effects) of 42.9% (95% confidence interval [CI]: 29.0%-58.0%). A separate subgroup analysis in symptomatic patients only again revealed a relatively high summary proportion of false positive follow-up FDG-PET of 37.5% (random effects). In conclusion, the false-positive proportion of follow-up FDG-PET in lymphoma patients who initially achieved an end-of-treatment complete remission is high and remains high when a combination of clinical symptoms and follow-up FDG-PET is used. Therefore, biopsy remains compulsory and follow-up FDG-PET alone may be regarded as unreliable to define progression-free survival.