Abstract Introduction Thyroglossal duct (TGD) carcinoma is an uncommon entity, located in the TGD remnant, and is diagnosed in patients undergoing evaluation of the neck for midline swelling, or incidentally after removal of a TGD cyst. Despite the presence of multiple publications on the topic, no systematic characterization of these tumors has been performed to date. The present study aims to characterize the tumors found patients diagnosed with TGD remnant malignancies. Methods We performed a systematic search for the term "Thyroglossal duct" in Pubmed, Embase and Cochrane databases on December 1, 2021 and retrieved 1229 records. We included all manuscripts containing cohorts, case reports or case series, when the manuscript or its abstract was available in English, Italian, French or Spanish language. We reviewed the demographics, the histological report of the thyroglossal duct and the thyroidectomy specimen (when this was performed) and the features of tumor aggressiveness, when these were available. Results We incorporated data from 366 manuscripts, comprising 1202 patients operated for TGD disease. Out of these, n=550 cancers were identified, consisting of n=475 (86.4%) Papillary thyroid carcinomas (PTC), n=8 Follicular thyroid carcinomas (FTC) (1.5%), n=5 Hürthle cell carcinomas (HCC) (0.9%), n=27 Squamous cell carcinomas (SCC) (4.9%), n=2 poorly differentiated/anaplastic thyroid carcinomas (ATC) (0.4%), n=1 Adeno-SCC (0.18%), n=1 Adenocarcinoma (0.18%), n=12 synchronous PTC/FTC (2.2%), n=1 synchronous PTC/SCC (0.18%) and n=18 of unclear histological diagnosis (4.75%). N=173/446 (38.8%) patients were males and n=273/446 (61.2%) were females; gender was not available in n=104 cases. Mean cancer size was 1.4±1.4cm (range 0.01-7.0cm); n=88/173 (50.9%) were microcarcinomas (<1cm). Distant metastasis was present in n=7 patients (1.3%). Lymph node involvement was reported in n=76/286 cases (26.6%); extrathyroidal extension was present in n=75/234 cases (32.1%); capsular invasion was present in 72/142 cases (50.7%). Adjuvant therapy with I-131 was used in n=131/550 cases (23.8%). Conclusions TGD remnant cancers include various tumors, with histology and features of aggressive behavior similar to what we see in thyroid cancer cases. More research is needed to enhance our understanding of the mechanisms involved in the pathogenesis and malignant behavior of these infrequently identified tumors. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.