Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, have demonstrated promising efficacy in the management of obesity and type 2 diabetes mellitus. While their association with medullary thyroid carcinoma (MTC) has been documented in preclinical studies, the relationship between GLP-1 RAs and differentiated thyroid carcinomas, particularly papillary thyroid carcinoma (PTC), remains unclear. We present a case of rapidly progressive PTC in a patient shortly after initiating semaglutide for weight loss. Case Presentation: A 35-year-old woman with a history of obesity and prior bariatric surgery presented with a rapidly enlarging anterior neck mass five weeks after initiating semaglutide (0.25 mg weekly). No previous thyroid abnormalities had been documented. Ultrasonography revealed a 6.8 cm solid, hypoechoic nodule in the right thyroid lobe, and fine-needle aspiration (FNA) confirmed features consistent with aggressive PTC. Despite recommendations for urgent surgical intervention, the patient deferred thyroidectomy for six months in favor of dietary management. Discussion: Although GLP-1 RAs can activate GLP-1 receptors on thyroid C-cells and have been associated with MTC in rodent models, their role in the pathogenesis or progression of PTC is poorly understood. The temporal association and atypically rapid tumor growth in this case raise concerns regarding a potential link between GLP-1 RA therapy and accelerated PTC progression. Conclusion: This case highlights the need for further investigation into the potential impact of GLP-1 receptor agonists on differentiated thyroid cancers, particularly in patients with no preexisting thyroid disease.