1668 Objectives Neuroendocrine tumors (NET) are a heterogeneous group of neoplasias, ranging from well-differentiated slow growing tumors, to poorly differentiated malignancies with more aggressive behavior. Tumor heterogeneity is present in many malignancies, including NETs. The aim of this communication is to emphasize the emerging role of combined molecular imaging (68Ga-DOTATATE and 18FDG) in NETs, assessing intra-tumoral heterogeneity. Methods We present two cases of intra-tumoral heterogeneity referred to our department for the evaluation of peptide receptor radionuclide therapy. Case number 1: a 66 year-old male patient with a pulmonary NET (Ki67 index of 10-15%) with synchronous hepatic metastases (Ki67 index of 5%). Case number 2: a 58 year-old male patient with a mesenteric NET, with multiple synchronous hepatic metastases (Ki67 index of 5-10%). Combined 68Ga-DOTATATE and 18FDG PET/CT were performed as part of the pre-therapeutic diagnostic work-up. Results Different tracer uptake was found in the pulmonary mass (case 1) and in the large hepatic lesion of the left lobe (case 2). This unusual pattern of intra-tumoral heterogeneity seems to indicate a better differentiation of the neuroendocrine tumour (overexpressing somatostatin receptors) in the areas of 68Ga-DOTATATE uptake, whilst the areas with high 18FDG uptake suggest a more aggressive tumor behavior, evoking the possibility of treatment resistant clones development. Conclusions Different parts in the same tumor, can demonstrate different grades of tracer uptake indicating different tumor biology, and hence different aggressiveness. Combined whole-body molecular imaging using both 68Ga-DOTATATE and 18FDG tracers, may highlight intra-tumoral heterogeneity, especially in the clinically challenging grade 2 NETs. This differential uptake may identify the more aggressive portion of the lesions allowing a more accurate molecular imaging guided biopsy.