Objectives: This study aimed to investigate the contributory role of histogram-based textural features (HBTFs) extracted from18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in tumoral heterogeneity (TH) evaluation and invasive lung adenocarcinoma (ILA) prognosis prediction. Methods: This retrospective study analyzed the data of 72 patients with ILA who underwent18F-FDG PET/CT followed by surgical resection. The maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis values were calculated for each tumor. Additionally, HBTFs were extracted from18F-FDG PET/CT images using the software program. ILA was classified into the following five histopathological subtypes according to the predominant pattern: Lepidic adenocarcinoma (LA), acinar adenocarcinoma, papillary adenocarcinoma, solid adenocarcinoma (SA), and micropapillary adenocarcinoma (MA). Differences between18F-FDG PET/CT parameters and histopathological subtypes were evaluated using non-parametric tests. The study endpoints include overall survival (OS) and progression-free survival (PFS). The prognostic values of clinicopathological factors and18F-FDG PET/CT parameters were evaluated using the Cox regression analyses. Results: The median SUVmax and entropy values were significantly higher in SA-MA, whereas lower in LA. The median energy-uniformity value of the LA was significantly higher than the others. Among all parameters, only skewness and kurtosis were significantly associated with lymph node involvement status. The median values for follow-up time, PFS, and OS were 31.26, 16.07, and 20.87 months, respectively. The univariate Cox regression analysis showed that lymph node involvement was the only significant predictor for PFS. The multivariate Cox regression analysis revealed that higher SUVmax (≥11.69) and advanced stage (IIB-IIIA) were significantly associated with poorer OS [hazard ratio (HR): 3.580, p=0.024 and HR: 7.608, p=0.007, respectively]. Conclusion: HBTFs were tightly associated with clinicopathological factors causing TH. Among the18F-FDG PET/CT parameters, only skewness and kurtosis were associated with lymph node involvement, whereas SUVmax was the only independent predictor of OS. TH measurement with HBTFs may contribute to conventional metabolic parameters in guiding precision medicine for ILA.