The aim of the present study was to investigate in detail the variation of the intrinsic spatial resolution across the useful field of view (UFOV) of gamma-cameras and to explore whether this variation could lead to observable effects in clinical images. Two gamma-cameras were used, without their collimators, to acquire 560 (99m)Tc point source images at different points across their UFOVs, in order to measure the intrinsic spatial resolution at each point. Possible clinical effects of the resolution variation were examined on images of a thyroid phantom using a LEHR collimator, acquired at different locations on the UFOV and at various distances from the collimator. The gamma-camera intrinsic resolution varied significantly across the UFOV, being generally lower at the central region and deteriorating at the edges. Pronounced local maxima and minima were found at points corresponding to the centers of the photomultiplier tubes (PMTs) and halfway in between. Maximum differences of more than 50% were observed between the points presenting the best and worst intrinsic resolution. Differences between neighboring points reached 17%. The effects of resolution variation were clearly observable on the thyroid phantom images. It was concluded that an appropriate correction algorithm might be necessary in order to correct for the variation of the intrinsic spatial resolution across the UFOV of gamma-cameras.