In dialysis patients β-thalassemia is a cause of resistance to erythropoietin (EPO). The aim of the present study is to evaluate the relationship between the amount of circulating anomalous hemoglobin chain and EPO resistance in hemodialysis. Ten hemodialyzed patients with β-thalassemia minor were studied. The mean hemoglobin level was 9.22 ± 0.91 g/dl, the HbA<sub>2</sub> ranging between 5.6 and 6.8%; the weekly EPO dose was 13,500 ± 7,185 IU/week and significantly correlated with HbA<sub>2</sub> (r = 0.965; p = 0.0001). When stratifying patients in two groups according to HbA<sub>2</sub> level (LOW <6%, n = 4; HIGH >6%, n = 6; HbA<sub>2</sub> levels, respectively, 5.7 ± 0.1 and 6.4 ± 0.3 g/dl, p = 0.002), it was evidenced that the need of EPO was 13,200 ± 3,033 IU/week in LOW and 36,167 ± 13,060 IU/week in HIGH (p < 0.001). The EPO Resistance Index in the two groups was 13.4 ± 4.1 IU/kg BW/week/g Hb in LOW and 21.9 ± 10.0 in HIGH (p < 0.05). No differences were evidenced between the two groups regarding age, dialysis, body weight, serum levels of urea nitrogen, creatinine, albumin, C-reactive protein, aluminum, ferritin, transferrin and parathyroid hormone. In conclusion, in patients with β-thalassemia minor on chronic hemodialysis, the amount of anomalous hemoglobin chain directly correlate with EPO dose, strongly indicating the magnitude of resistance to erythropoietin.