We present a case of high-dose dextromethorphan ingestion with associated rapid urine drug screening and confirmatory testing demonstrating an apparent false-positive opiates screen. Further testing was performed using alternative screening assays and analysis of drug-free matrices spiked with various concentrations of dextromethorphan and its metabolite, dextrorphan. Results demonstrate a subset of urine opiates screening assays may be susceptible to dextromethorphan cross-reactivity at high concentrations.