The link between specific circulating tumor cell (CTC) phenotypes or genotypes and the effectiveness of neoadjuvant chemotherapy (NAC) has not been clearly established. This investigation aimed to determine whether FTH1 gene–related CTCs (F-CTC), with or without epithelial–mesenchymal transition (EMT) markers, as well as their temporal variations, are associated with NAC outcomes in patients with non-metastatic breast cancer. A total of 120 patients with non-metastatic breast cancer scheduled for NAC were included. Detection of the FTH1 gene and EMT markers in CTCs was performed before NAC (T0), after two chemotherapy cycles (T1), and prior to surgery (T2). Binary logistic regression was applied to analyze the associations between different CTC subtypes and rates of pathological complete response (pCR) and breast-conserving surgery (BCS). The presence of ≥1 F-CTC in peripheral blood at T0 was identified as an independent predictor of pCR in patients with HER2-positive disease (odds ratio [OR] = 0.08, 95% confidence interval [CI], 0.01–0.98, P = .048). A decrease in F-CTC counts at T2 independently predicted a higher likelihood of BCS (OR = 4.54, 95% CI, 1.14–18.08, P = .03). Elevated F-CTC levels before NAC were associated with an unfavorable response to NAC. Continuous assessment of F-CTC may assist clinicians in tailoring individualized NAC strategies and facilitating BCS in patients with non-metastatic breast cancer.