A false-positive complement-dependent cytotoxicity cross-match (CDC XM) has a negative impact in donor selection process obliterating healthy, donor compatible population. A 47-year-old male with chronic kidney disease was planned for ABO-compatible renal transplantation from his sister. CDC and donor-specific antibody (DSA) lysate XM were negative 10 days before transplant. The pretransplant CDC XM showed 40% positivity. DSA lysate XM and HLA antibody screen were negative. Patient's Indirect antiglobulin test (IAT) was positive and anti-M antibody (IgG + IgM) was identified. Therapeutic plasma exchange, intravenous immunoglobulin, and rituximab were used for desensitization. Decrease in positivity of CDC XM and anti-M titer was seen. The transplant was performed successfully. Red cell alloantibody should be considered in differential diagnosis of a positive CDC XM. The utility of DSA lysate XM as a pretransplant monitoring tool is immense in such situations. Institutional policies regarding plan of action in the event of positive CDC XM and negative DSA lysate XM and vice versa should be formed.