CYP2D6duplication has important pharmacogenomic implications. Reflex testing with long-range PCR (LR-PCR) can resolve the genotype when a duplication and alleles with differing activity scores are detected. We evaluated whether visual inspection of plots from real-time-PCR-based targeted genotyping with copy number variation (CNV) detection could reliably determine the duplicatedCYP2D6allele. Six reviewers evaluated QuantStudio OpenArrayCYP2D6genotyping results and the TaqMan Genotyper plots for seventy-three well-characterized cases with three copies ofCYP2D6and two different alleles. Reviewers blinded to the final genotype visually assessed the plots to determine the duplicated allele or opt for reflex sequencing. Reviewers achieved 100% accuracy for cases with threeCYP2D6copies that they opted to report. Reviewers did not request reflex sequencing in 49–67 (67–92%) cases (and correctly identified the duplicated allele in each case); all remaining cases (6–24) were marked by at least one reviewer for reflex sequencing. In most cases with three copies ofCYP2D6, the duplicated allele can be determined using a combination of targeted genotyping using real-time PCR with CNV detection without need for reflex sequencing. In ambiguous cases and those with >3 copies, LR-PCR and Sanger sequencing may still be necessary for determination of the duplicated allele.