Hematologic malignancies represent a vast group of hematopoietic and lymphoid cancers that typically involve the blood, the bone marrow, and the lymphatic organs. Due to extensive research and well defined and standardized response criteria, the role of 18FFDG-PET/CT is well defined in these malignancies. Never the less, the reliability of visual and quantitative interpretation of PET/CT may be impaired by several factors including inconsistent scanning protocols and image reconstruction methods. Furthermore, the uptake of 18FFDG not only reflects tissue glucose consumption by malignant lesions, but also in other situations such as in inflammatory lesions, local and systemic infections, benign tumors, reactive thymic hyperplasia, histiocytic infiltration, among others; or following granulocyte colony stimulating factors therapy, radiation therapy, chemotherapy or surgical interventions, all of which are a potential source of false-positive or negative interpretations. Therefore it is of paramount importance for the Nuclear Medicine Physician to be familiar with, not only the normal distribution of 18FFDG in the body, but also with the most frequent findings that may hamper a correct interpretation of the scan, which could ultimately alter the patients management. In this review, we describe these myriad of situations so the interpreting physician can be familiar with them, providing tools for their correct identification and interpretation when possible.