Abstract Background Activating mutations of the EGFR gene in lung carcinoma are associated with response to tyrosine kinase inhibitors. Therefore, a rapid, sensitive assay for mutation detection using routine pathological specimens is mandatory in clinical practice. Methods We have compared our in-house procedure to the Therascreen® EGFR RGQ PCR kit (Qiagen). This assay, based on allele-specific amplification, is approved in the United States, in Europe, Japan and China. Results We first selected a series of 209 that were representative of our routine practice during the last 2years. Using our assays, EGFR mutations were detected in 36 (17.4%) of these patients (18 p.L858R mutations and 18 exon 19 deletions). All these alterations were also detected using the Therascreen® kit. In addition, this kit allowed us to detect 7 additional alterations: one exon 19 alteration (c.2239_2240TT>CC, p.L747P), 3 p.G719X mutations and 3 p.S768L mutations. In the second part of our study, we selected 81 samples that were identified as deleted for exon 19 using our assay. Eighteen different deletions were described following sequencing. All these samples were tested positive with the Therascreen® kit. Conclusion The Therascreen® EGFR RGQ kit was found to be very powerful (sensitivity 100%; specificity 100%) for the detection of the most frequent EGFR alterations that are clearly associated with response to tyrosine kinase inhibitors.