Herein, we present six patients with high-oxygen-affinity Hb variants, either in heterozygous form or in compound heterozygosity (such as heterozygosity for Hb Hiroshima, Köln, Crete, and compound heterozygosity Hb Crete with β or δβ thalassemia), in order to demonstrate the need for prompt and accurate diagnosis and enrich the limited literature due to the rarity of such cases. The gene discussed is GSTM1; the disease is thalassemia.