Thyroid tumors are the most common endocrine malignancies worldwide [1]. In recent years, the incidence of thyroid cancer has been increasing, and PTC is the most diagnosed thyroid tumor, accounting for 80 %–90 % of all thyroid cancers [2,3]. For the clinical diagnosis of thyroid cancer, ultrasound-guided FNAC is a routine method for evaluating thyroid nodules. Although most patients are diagnosed by FNAC, approximately 15 %–30 % of thyroid nodules remain diagnostically challenging on fine-needle aspiration specimens [4]. The 2015 American Thyroid Association guidelines recommend that molecular testing can be used to reduce the frequency of repeat fine-needle aspiration cytology and the rate of unnecessary surgery in patients with indeterminate cytology. Molecular detection of BRAF V600E mutations in preoperative puncture specimens can help improve the rate of confirmed diagnosis [5,6]. However, the sample volume of fine needle aspiration is sometimes insufficient for molecular testing. Additionally, the detection period is long, and molecular testing is expensive for most patients in China [7]. Therefore, seeking new biomarkers for the diagnosis of thyroid cancer is significant in the diagnosis and treatment of thyroid tumors.

EphB3 is a member of the largest family of receptor tyrosine kinases, Eph [8]. According to their homology in sequence and binding affinity to membranes, Eph receptors are classified into classes A and B [9]. EpB/ephrin-B plays an important role in many diseases [10], and it is closely related to cancer-related activities, with its surface enhanced or diminished depending on the tumor type [11,12]. EphB3 is expressed in various tumors, including colorectal cancer, lung cancer, and bladder cancer [[13], [14], [15]]. EphB3 expression is downregulated in colorectal cancer cells, and hypermethylation of the EphB3 promoter may be involved in the down-regulation of expression [16]. The expression of EphB3 is upregulated in squamous cell lung cancer, which promotes cancer cell proliferation and migration [14]. EphB3 shows low expression in bladder cancer and can be used as a predictive marker for bladder cancer muscle invasion [15]. Moreover, EphB3 has been shown to stimulate cell migration and metastasis in a kinase-dependent manner through the Vav2-Rho GTPase axis in papillary thyroid carcinoma [17]. We previously reported the expression and clinicosignificance of EphB3 in ovarian and colorectal cancers [16,18]. In this study, the expression of EphB3 in normal thyroid tissues and thyroid tumor tissues was investigated using immunohistochemical staining.