The P blood group system was introduced in 1927 by Landsteiner and Levine. About 75% of the population possesses P1 phenotype. P2 simply implies P1 negative and there is no P2 antigen. Individuals with P2 may have anti-P1 antibodies in there serum are cold-reacting antibodies which are clinically insignificant and occasionally active at 20°C or higher temperatures. However, in certain cases, anti-P1 is clinically significant and may cause acute intravascular hemolytic transfusion reactions. Our case report confirms the complexity and difficulty in the diagnosis of anti-P1. In India, very few cases are reported regarding clinical significant anti-P1. Here, we report a case of IgM type of antibody anti-P1 which was reactive at 37°C and AHG phase in a 66-year-old female planned for Whipple's surgery, who had grouping discrepancies in reverse typing and incompatibility during routine crossmatch.