Background and Aims The incidence of papillary thyroid carcinoma (PTC) has shown a significant upward trend. Given its favorable prognosis, there is a growing trend toward de-escalating its treatment to improve patients' quality of life. Pathologists have renamed the encapsulated follicular variant of PTC with indolent biological behavior as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), providing a theoretical basis for treatment de-escalation. However, challenges persist in the clinical pathological diagnosis of NIFTP, and it is still predominantly managed as classical PTC in most cases. This study was performed to explore the clinicopathologic diagnostic characteristics, surgical challenges, and prospects for de-escalation treatment of NIFTP.Methods The clinical data of 33 patients with thyroid disease who were admitted to Xuanwu Hospital Capital Medical University from November 2017 to December 2022 and confirmed as NIFTP by final paraffin pathology were retrospectively analyzed.Results Among the 33 NIFTP patients, there were 11 males and 22 females, with an average age of 50 years. Tumor sizes ranged from 0.6 to 7.5 cm. There were 31 cases of solitary NIFTP tumor and 2 cases of multifocal tumors (each involving 2 sites). Eleven patients had coexisting PTC (one lesion in each case), with 4 lesions located on the same side as the NIFTP and 7 on the opposite side. All patients underwent surgical treatment, including 27 cases of conventional open surgery and 6 cases of endoscopic surgery. Suspicious or potentially malignant lesions were treated according to PTC surgical principles (lobectomy of the affected side plus central compartment lymph node dissection on the same side). Preoperative ultrasonography revealed that the nodules were predominantly hypoechoic, relatively regular in shape, well-defined, often accompanied by calcifications, and had a longitudinal-to-transverse diameter ratio of <1. TI-RADS classifications were as follows: 5 cases as grade 3, 9 cases as grade 4a, and 11 cases as grade 4b or higher. Among 29 patients who underwent preoperative fine-needle aspiration, 1 case was diagnosed as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 12 as follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 12 as suspicious for malignancy (SUS), and 4 as PTC. BRAF^V600E mutation testing was performed postoperatively in 25 cases, and 7 mutations were detected, all in cases with concomitant PTC.Conclusion The introduction of the NIFTP concept provides a foundation for de-escalation or individualized treatment of certain less aggressive thyroid tumors. However, the preoperative and intraoperative diagnosis of NIFTP remains challenging in clinical practice. More precise preoperative diagnostic criteria and methods are needed to enable surgeons to adjust treatment decisions accordingly.