Aim: CYP2D6*2 is considered fully active, but it has been suggested that it only happens in the presence of rs5758550. This study aims to elucidate the impact of this enhancer. Materials & methods: DNA and blood samples from women enrolled in the CYPTAM study (NTR1509) were analyzed. Fourteen CYP2D6*2 carriers without the enhancer were reclassified. The relationship of CYP2D6 phenotypes and drug levels was studied. Results: After correction for the absence of the enhancer, the correlation between CYP2D6 phenotypes and endoxifen did not improve (R²: 0.290 vs 0.279). No difference was observed in mean concentrations between CYP2D6*2 individuals with and without the enhancer. Conclusion: The rs5758550 enhancer does not lead to improved prediction of endoxifen levels in breast cancer patients.