Low-incidence antigens are known to occur in less than 1% of individuals in most populations. Alloantibodies against low-frequency antigens pose a risk of potential hemolytic transfusion reactions and hemolytic disease in fetuses and newborns. We describe a technique of “Nonspecific alloadsorption” to identify a suspected antibody to a low-frequency antigen in the presence of an interfering autoantibody. A 15-year-old thalassaemic reported to our blood bank with an inability to find compatible blood units. There was a presence of an allo-antibody with auto-antibody. We attempted a “non-specific allo adsorption” for identifying an interfering allo-antibody against a low-frequency antigen. Our case report highlights that understanding the basic antigenic frequencies of various antigens can play an important role in antibody identification. It is always important to exclude alloantibody when autoantibody or AIHA scenarios are presented in thalassemia patients for safe transfusions.