There are several irregular antibodies associated with various blood group systems which may cause some problems during blood cross matching in transfusion.The atypical antibodies are included auto and alloantibodies such as anti-I, anti-HI, anti-P... . In order to detect these antibodies, generally the agglutination REACTion technique and anti-human-globulin (coombs) tests would be performed and a panel of identified red blood cells will use if necessary for further investigation.During our work, we encountered with one serum sample that showed agglutination REACTion with all the blood groups (A, B, O, and AB).We tested pooled red blood cells with OI group of adult and pooled cord red blood cells of Oi group with the patient serum. It was shown that the serum was REACTive with 01 but not with Oi. For confirmation of the result, the sample was sent to Institute of Immunohematology (I.I.H.), India. The report approved that the serum contained anti-I specificity. To solve the transfusion problem for this patient, the recommendation is using the blood group with minimum coombs titration if the patient life is in threatened. Further investigations disclosed that the patient had leukemia.