A C>G mutation at position 6 3′ to the terminating codon was first described several years ago in a young Greek patient with β-thalassemia intermedia. This mutation was identified in a further nine Greekβ-thalassemia intermedia patients, compound heterozygous for common severe β-thalassemia determinants. We present the clinical and hematological phenotype in the patients and in their β+6 heterozygote parents. All β-thalassemia genotypes were defined by ARMS or DGGE and direct sequencing. β-gene cluster haplotypes were characterized with standard PCR-based protocols. Three of the patients were diagnosed during adolescence; the remaining six were diagnosed in childhood (mean age 9 years). None required transfusion. They have satisfactory development, mildly thalassemic appearance and present with moderate splenomegaly; three of them have been splenectomized. They preserve hemoglobin levels around 9 g/dl and HbF below 25% (mean 12%). The β-gene cluster haplotype of the chromosome with the +6 to termination C>G mutation was characterized as VI for 5/9 of the patients and VII for 2/9. In two, the haplotype could not be defined. The carriers of this mutation are clinically and hematologically silent with slightly unbalanced globin chain synthesis (mean values: Hb 13.5 g/dl, Ht 42%, MCV 88.6 fl, MCH 27.7 pg, HbA2 2.67%, HbF 1.05%, α/nona:1.63). This mutation was observed in 9/33 β-thalassemia/ β-silent mild intermedia patients. Thus this mutation is a common cause underlying the silent β-thalassemia heterozygous phenotype in Greece. In the compound heterozygous state with common β-thalassemia mutations it results in the clinical phenotype of mild non-transfusion dependent thalassemia intermedia.