Objectives: Since the introduction of the entity of “Atypical cell of undetermined significance /follicular lesion of undetermined significance” (AUS/FLUS) by The Bethesda System for Reporting Thyroid Cytology (TBSRTC) in 2007, there have been many published studies about the cytomorphologic criteria, subclassification, outcome, and management of patients with the diagnosis of AUS/FLUS. There have been many studies in different aspects of this indeterminate category, i.e., cytologic and molecular findings, ultrasonographic findings, and in some instances even core-needle biopsy to address a better and safer way of the management of patients with this fine-needle aspiration cytology diagnosis. The second edition of TBSRTC and the 2015 American Thyroid Association guidelines provide an update on the follow-up and management of AUS/FLUS. A multidisciplinary team consisting of pathologists, endocrinologists, surgeons, and radiologists should be involved in the diagnosis and management of AUS/FLUS, and all of them should be aware of the heterogeneity of this lesion for the prediction of the treatment and outcome. Study Design: In this review, we consider different research platforms (2008–2017) to find the best and key reports for the above-mentioned challenging aspects of AUS/FLUS. Conclusion: AUS/FLUS is now a well-defined group of thyroid lesions, which can be most accurately diagnosed and managed with cytomorphology, molecular, and ancillary studies.

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