Background There is increasing interest in applying image texture quantifiers to assess the intra-tumor heterogeneity observed in FDG-PET images of various cancers. Use of these quantifiers as prognostic indicators of disease outcome and/or treatment response has yielded inconsistent results. We study the general applicability of some well-established texture quantifiers to the image data unique to FDG-PET. Methods We first created computer-simulated test images with statistical properties consistent with clinical image data for cancers of the uterine cervix. We specifically isolated second-order statistical effects from low-order effects and analyzed the resulting variation in common texture quantifiers in response to contrived image variations. We then analyzed the quantifiers computed for FIGOIIb cervical cancers via receiver operating characteristic (ROC) curves and via contingency table analysis of detrended quantifier values. Results We found that image texture quantifiers depend strongly on low-effects such as tumor volume and SUV distribution.When low-order effects are controlled, the image texture quantifiers tested were not able to discern only the second-order effects. Furthermore, the results of clinical tumor heterogeneity studies might be tunable via choice of patient population analyzed. Conclusion Some image texture quantifiers are strongly affected by factors distinct from the secondorder effects researchers ostensibly seek to assess via those quantifiers.