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Background  PET image reconstruction methods include modeling of resolution degrading phenomena, often referred to as point-spread function (PSF) reconstruction. The aim of this study was to develop a clinically relevant phantom and characterize the reproducibility and accuracy of high-resolution PSF reconstructed images of small lesions, which is a prerequisite for using PET in the prediction and evaluation of responses to treatment.  Sets of small homogeneous  18 F-spheres (range 3–12 mm diameter, relevant for small lesions and lymph nodes) were suspended and covered by a  11 C-silicone, which provided a scattering medium and a varying sphere-to-background ratio. Repeated measurements were made on PET/CT scanners from two vendors using a wide range of reconstruction parameters. Recovery coefficients (RCs) were measured for clinically used volume-of-interest definitions.    Results  For non-PSF images, RCs were reproducible and fell monotonically as the sphere diameter decreased, which is the expected behavior. PSF images converged slower and had artifacts: RCs did not fall monotonically as sphere diameters decreased but had a maximum RC for sphere sizes around 8 mm, RCs could be greater than 1, and RCs were less reproducible. To some degree, post-reconstruction filters could suppress PSF artifacts.    Conclusions  High-resolution PSF images of small lesions showed artifacts that could lead to serious misinterpretations when used for monitoring treatment response. Thus, it could be safer to use non-PSF reconstruction for quantitative purposes unless PSF reconstruction parameters are optimized for the specific task.    Electronic supplementary material  The online version of this article (doi:10.1186/s40658-016-0169-9) contains supplementary material, which is available to authorized users.

Point-spread function reconstructed PET images of sub-centimeter lesions are not quantitative