Thyroglobulin antibody (TgAb) is a diagnostic serological marker of Hashimoto's thyroiditis (HT). The pathogenesis of HT progression from euthyroidism to hypothyroidism is still not clear. Epitope recognition patterns of TgAb have been shown to be different in individuals who are euthyroid or who have clinical disease. The aim of our study was to investigate the role of thyroglobulin (Tg) epitope specificities in HT progression. Sera from 107 patients with newly diagnosed HT were collected and divided into three groups: patients with hypothyroidism (H, n = 39), subclinical hypothyroidism (sH, n = 31) and euthyroidism (Eu, n = 37). A panel of Tg murine monoclonal antibodies (mAb: PB2, 5E6, 1D4, 5F9, Tg6) and a hircine pAb (N15) were employed as the probe antibodies to define the antigenic determinants recognized by HT sera on competitive enzyme-linked immunosorbent assays (ELISAs). Eight of 39 sera samples in H and seven of 31 in sH inhibited PB2 binding, respectively, whereas none did in Eu. The ratio of sera samples, inhibiting PB2 binding in Eu, was significantly lower than that in H (P = 0·011) and in sH (P = 0·008). For N15, five of 39 sera samples in H, six of 31 in sH and 15 of 37 in Eu inhibited its binding, respectively. The ratio of sera samples, inhibiting N15 binding in Eu, was significantly higher than that in H (P = 0·013). Our study demonstrated that HT patients in different thyroid functional status exhibited different Tg epitope recognition patterns. Epitope patterns of TgAb might be used as a prediction marker of HT progression.