Anti-M is a fairly common naturally occurring antibody with rarely causing hemolytic transfusion reactions or hemolytic disease of the newborn. Most anti-M are not active at 37 o C and can generally be ignored in transfusion practice. However, we did not find this antibody to be fairly common and detected only two cases of anti-M in the past three years. We describe these two cases; one ′immunizing′ type and other ′naturally occurring′ and review the literature. The immunizing type was reactive at 37 o C as well as AHG phase of testing with IgG component, and showing dosage effect while the other was ′naturally occurring′ reactive well below 37 o C. Though rare, sometimes these antibodies can be of clinical significance when the antibody detected is reactive at 37 o C and AHG phase. When the antibody is active at 37 o C, M antigen negative cross match compatible red cell unit should be given.